JP4042683B2 - Microchannel structure and microparticle manufacturing method using the same - Google Patents

Microchannel structure and microparticle manufacturing method using the same Download PDF

Info

Publication number
JP4042683B2
JP4042683B2 JP2003386796A JP2003386796A JP4042683B2 JP 4042683 B2 JP4042683 B2 JP 4042683B2 JP 2003386796 A JP2003386796 A JP 2003386796A JP 2003386796 A JP2003386796 A JP 2003386796A JP 4042683 B2 JP4042683 B2 JP 4042683B2
Authority
JP
Japan
Prior art keywords
channel
dispersed phase
continuous phase
flow path
phase
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
JP2003386796A
Other languages
Japanese (ja)
Other versions
JP2005144356A (en
Inventor
達 二見
朋裕 大川
明 川井
英昭 桐谷
晃治 片山
恵一郎 西澤
裕樹 高宮
Original Assignee
東ソー株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 東ソー株式会社 filed Critical 東ソー株式会社
Priority to JP2003386796A priority Critical patent/JP4042683B2/en
Publication of JP2005144356A publication Critical patent/JP2005144356A/en
Application granted granted Critical
Publication of JP4042683B2 publication Critical patent/JP4042683B2/en
Application status is Active legal-status Critical
Anticipated expiration legal-status Critical

Links

Images

Description

  The present invention relates to microparticles used in preparative / separation column fillers and microparticles used in microcapsules used in pharmaceuticals, enzyme-containing capsules, cosmetics, fragrances, display / recording materials, adhesives, agricultural chemicals, and the like. The present invention relates to a microchannel structure suitable for generation and a method for producing microparticles using the microchannel structure.

  In recent years, a fluid is introduced into a microchannel using a microchannel structure having a microchannel having a length of about several centimeters on a glass substrate of several cm square and a width and depth of sub-μm to several hundred μm. Research has been attracting attention for the production of microparticles, and the creation of microparticles by introducing two types of liquids with different interfacial tensions into the channel where the intersection of the two types of fluid exists. (For example, refer to Patent Document 1 and Non-Patent Document 1). The microparticles here are solid microparticles, microdroplets, microparticles obtained by curing only the surface of microdroplets (hereinafter referred to as “semi-cured”), and extremely high viscosity. Also includes semi-solid fine particles.

  For example, the technique shown in Patent Document 1 or Non-Patent Document 1 is shown in FIG. 1 and FIG. 2, which is a partial cross-sectional view of the flow path thereof, as shown in FIG. A flow path for introducing a continuous phase (hereinafter referred to as continuous phase introduction flow path (3)), a dispersed phase introduction port (4), a flow path for introducing a dispersed phase (hereinafter referred to as dispersed phase introduction flow path (5)), It has a T-shaped channel having a channel (hereinafter referred to as “discharge channel (7)”) and a discharge port (8) for discharging the dispersed phase into microparticles in the continuous phase, and the channel surface side of the substrate Is a micro-channel structure in which a cover body is joined to the continuous phase, and the dispersed phase is discharged from the dispersed phase supply port in a direction intersecting the flow of the continuous phase with respect to the continuous phase flowing in the microchannel, and the continuous phase is sheared Due to the force, micro droplets having a diameter smaller than the width of the supply channel of the dispersed phase are obtained. Here, the width of the continuous phase introduction flow path which is a microchannel is described as 100 μm in Patent Document 1 and 500 μm in Non-Patent Document 1. In addition, the width of the dispersed phase introduction channel through which the dispersed phase flows is 100 μm in both Patent Document 1 and Non-Patent Document 1, and the depth of the continuous phase introduction channel, which is a microchannel, and the dispersed phase introduction channel through which the dispersed phase flows. The depth of both is 100 μm in both Patent Document 1 and Non-Patent Document 1. Hereinafter, the portion where the introduced continuous phase and the dispersed phase intersect is hereinafter referred to as the intersection (6). In Patent Document 1 and Non-Patent Document 1, the continuous phase introduction flow path is described as a microchannel, but the dispersed phase introduction flow path is not particularly described as a microchannel. When this method is used and liquid feeding is performed by controlling the flow rates of the dispersed phase and the continuous phase, it is possible to generate micro droplets of several hundred μm or less. In addition, it is possible to control the particle size of the fine droplets generated by controlling the flow rates of the dispersed phase and the continuous phase. Regarding the particle diameter of the obtained microdroplets, in Patent Document 1, the liquid feeding pressure of the dispersed phase is fixed to 2.45 kPa, and the liquid feeding pressure of the continuous phase is changed to 4.85 to 5.03 kPa. It is shown that microdroplets with a particle size of ˜25 μm are obtained. Further, in Non-Patent Document 1, microdroplets having a particle size of about 80 μm minimum to about several hundred μm maximum are obtained by changing the liquid feeding pressure of the dispersed phase and the continuous phase in the range of about 20 to about 250 kPa. It is shown.

  However, Patent Document 1 and Non-Patent Document 1 described above do not describe at all the particle size distribution (hereinafter referred to as particle size dispersion) of the generated microdroplets. Here, the particle size dispersion is defined as a value obtained by dividing the standard deviation of the particle size by the average value of the particle size (hereinafter referred to as the average particle size). Therefore, when the present inventors actually conducted an experiment to produce a microdroplet by producing a microchannel structure similar to the microchannel structure described in Patent Document 1 and Non-Patent Document 1, Certainly, microdroplets having an average particle size of several tens of μm to several hundreds of μm could be obtained, but the particle size dispersion of the generated microdroplets was not satisfactory at 20 to 30% or more. In particular, fine droplets (hereinafter referred to as 20 to 30% or less of the average particle size) having a particle size of 20 to 30% or less of the average particle size of the obtained fine droplets. The first type of quasi-microdroplet is referred to as a first type quasi-microdroplet, and the microdroplet having a particle diameter of less than 10 μm is referred to as a second-type quasi-microdroplet. The two types of quasi-microdroplets are combined to form a quasi-microdroplet), and the presence of the quasi-microdroplets deteriorates the particle size dispersion, and improvements to improve the particle size dispersion are desired. It was done. In the present invention, “good particle size dispersion” means that the particle size dispersion is less than 10%.

WO02 / 068104

Takashi Nishisako et al., "Liquid microdroplet generation in microchannels", Proceedings of the 4th Chemistry and Microsystem Study Group, 59 pages, 2001

  As described above, the problem of microparticle generation in the flow channel according to the prior art is that the particle size dispersion degree is less than 10% at the intersection between the dispersed phase flowing in the microchannel and the continuous phase. This is to generate fine particles, and in particular, to prevent the generation of quasi-micro droplets having a particle size of about 20 to 30% or less of the average particle size.

  The object of the present invention has been made in view of the above problems, and the particle size dispersion degree of the microparticles generated in the flow path at the intersection between the dispersed phase flowing in the microchannel and the continuous phase is less than 10%. An object of the present invention is to provide a microchannel structure that generates microparticles having a uniform particle diameter and a microparticle manufacturing method using the microchannel structure.

  The microchannel structure of the present invention that solves the above problems includes an inlet for introducing a dispersed phase and a dispersed phase introducing channel, an inlet for introducing a continuous phase and a continuous phase introducing channel, and a dispersion A microchannel structure comprising a channel having a discharge channel and a discharge port for discharging microparticles generated by a phase and a continuous phase, the dispersed phase flowing in the microchannel On the other hand, the continuous phase is discharged from the continuous phase supply port in a direction intersecting the flow of the dispersed phase at an arbitrary angle, and fine particles are generated from the dispersed phase by the shearing force of the continuous phase and the wall surface in the flow path. A fine channel structure characterized by controlling the diameter of the fine particles.

  Further, the depth and / or width of the discharge channel from the intersection where the dispersed phase flowing in the microchannel intersects with the continuous phase intersects to the discharge port is larger than the depth and / or width of the channel through which the dispersed phase flows. It is a microchannel structure characterized by being large.

  Further, the position where the depth and / or width of the discharge flow path from the intersection where the dispersed phase and the continuous phase intersect to the discharge port is larger than the depth and / or width of the flow path through which the dispersed phase flows, A microchannel structure characterized in that the generated microdroplet is in a position before being decomposed into first-type quasi-microdroplets smaller than the microdroplets.

  In addition, the width of the discharge flow path is narrow at a part of the discharge flow path from the intersection where the dispersed phase flowing in the microchannel intersects the continuous phase to the discharge port, and the discharge flow path This is a microchannel structure characterized in that the portion where the width of the channel is narrow is at or near the intersection where the dispersed phase flowing through the microchannel intersects with the continuous phase.

  The microchannel structure characterized in that the part where the width of the discharge channel is narrow is on the dispersed phase introduction channel side of the intersecting portion where the dispersed phase flowing in the microchannel intersects with the continuous phase intersecting It is.

  Further, in the vicinity of the intersection where the disperse phase flowing in the microchannel intersects with the continuous phase, one or more protrusions are formed from the bottom surface, top surface, and / or side surface of the flow path. It is a road structure.

  The microparticle production method of the present invention is a microparticle production method for producing microparticles using a microchannel structure having any one of the forms described above, and further introduces a flow for introducing a dispersed phase. It is a method for producing microparticles characterized by controlling the particle size of microparticles generated by changing the angle at which a path and an introduction flow path for introducing a continuous phase intersect. Hereinafter, the present invention will be described in more detail.

  The microchannel used in the present invention generally indicates a channel having a width of 500 μm or less and a depth of 300 μm or less, and the microchannel may be referred to as a microchannel. In the following, the microchannel defined as described above and the channel having a width and depth larger than the microchannel may be collectively referred to as a channel. The discharge channel is substantially continuous with the continuous phase introduction channel, and the discharge channel exists as an extension of the continuous phase introduction channel. In the present invention, the dispersed phase introduction flow path is a microchannel, but the continuous phase introduction flow path is not particularly limited to a microchannel, and may be a microchannel or not a microchannel. Therefore, the discharge flow path substantially continuous with the continuous phase introduction flow path is not limited to the microchannel, and the discharge flow path may be a microchannel or not a microchannel. Rather, as will be described later, in order to improve the particle size dispersion of the fine particles, which is the object of the present invention, the continuous phase introduction flow path and the discharge flow path are preferably not microchannels, and in particular, the discharge flow paths are microchannels. More preferably not.

  Further, the fine particles in the present invention mean that the continuous phase is discharged from the continuous phase supply port in a direction intersecting the flow of the dispersed phase at an arbitrary angle with respect to the dispersed phase flowing in the microchannel, and the continuous phase and the flow. The fine particles are generated from the dispersed phase by the shearing force of the wall surface in the channel, and the size of the fine particles is generally smaller than the width or depth of the fine channel. For example, the size of a microparticle generated in a microchannel having a width of 100 μm and a depth of 50 μm is smaller than at least 100 μm, assuming that the microparticle is a perfect sphere. In addition to solid microparticles, the microparticles obtained by the present invention are microdroplets, semi-cured microparticles that are cured only on the surface of the microdroplets, and semisolid microparticles that are very viscous. Including.

  In addition, the dispersed phase used in the present invention is a liquid material for generating fine particles, for example, a monomer for polymerization such as styrene, a crosslinking agent such as divinylbenzene, and a gel for producing a gel such as a polymerization initiator. It refers to a medium in which raw materials are dissolved in a suitable solvent. Here, as the dispersed phase, the purpose of the present invention is to efficiently generate fine microparticles, and the microchannel in the microchannel structure can be fed to achieve this purpose. There is no particular limitation as long as it is fine, and the components are not particularly limited as long as fine particles can be formed. Further, it may be in the form of a slurry in which a solid phase such as a fine powder is mixed in the dispersed phase, or the dispersed phase may be a laminar flow formed from a plurality of fluids. It may be a mixed fluid formed from these fluids or a suspension (emulsion).

  In addition, the continuous phase used in the present invention is a liquid material used to generate fine particles by shearing the dispersed phase. For example, a dispersant for producing a gel of polyvinyl alcohol is dissolved in an appropriate solvent. Refers to the medium. Here, as in the case of the dispersed phase, the continuous phase is not particularly limited as long as it can feed the flow path in the micro flow path structure, and the component is not particularly limited as long as micro particles can be formed. Further, it may be a slurry in which a solid material such as a fine powder is mixed in the continuous phase, or the dispersed phase may be a laminar flow formed from a plurality of fluids. It may be a mixed fluid formed from these fluids or a suspension (emulsion). From the viewpoint of the composition of the fine particles to be generated, if the outermost layer of the fine particles is an organic phase, the outermost layer of the continuous phase is an aqueous phase, and if the outermost layer of the fine particles is an aqueous phase, the outermost layer of the continuous phase Becomes the organic phase.

  Further, it is more preferable that the dispersed phase and the continuous phase do not substantially cross each other or have no compatibility in order to generate fine particles. For example, when the aqueous phase is used as the dispersed phase, An organic phase such as butyl acetate that is substantially insoluble in water will be used. Moreover, the reverse is true when an aqueous phase is used as the continuous phase.

  The method for producing fine particles of the present invention introduces the above-mentioned dispersed phase and continuous phase from the respective introduction flow channels into the micro flow channel structure according to the present invention, which will be described later. In order to generate fine particles by shearing the wall surface in the channel, a dispersed phase introduction channel for introducing a dispersed phase flowing in the microchannel and a continuous phase introduction channel for introducing a continuous phase are introduced. It is possible to control the particle size of the generated microparticles by changing the angle at which the crosses. This is easier to control than the case of changing the introduction speed of the dispersed phase and the continuous phase in the generation of microparticles using the conventional microchannel structure, and is suitable for industrial mass production. In particular, if the introduction speed of the dispersed phase and the introduction speed of the continuous phase are substantially the same, it is excellent in terms of cost, for example, it is sufficient to prepare one introduction device. Note that the introduction rate of the dispersed phase and the introduction rate of the continuous phase here are substantially the same, even if there is some variation in the introduction rate of each phase, the particle size of the generated fine particles is greatly affected. This means that the particle size dispersion is not changed. By doing in this way, the microparticle of the stable particle size can be produced | generated. Further, it is not necessary to supply the continuous phase excessively. For example, the cost of the continuous phase in gel production can be reduced, and industrial mass production can be achieved.

  As a method of intersecting the dispersed phase introduction flow path of the dispersed phase flowing through the microchannel and the continuous phase introduction flow path through which the continuous phase flows in the present invention, basically a Y-shaped flow path as shown in FIG. , The dispersed phase is introduced from the dispersed phase introduction port (4), the continuous phase is introduced from the continuous phase introduction port (2), and the dispersed phase is separated from the continuous phase and the wall surface at the intersection (6) of the dispersed phase and the continuous phase. The fine particles (17) are generated by shearing by the shearing force of. However, the present invention is not limited to this method, and as shown in FIG. 7, the continuous phase (10) flows from both sides of the dispersed phase into the dispersed phase (15) flowing in the dispersed phase introduction flow path (5). A method of generating fine particles (17) by crossing so as to sandwich and shearing with a shearing force between the continuous phase and the upper and lower wall surfaces of the flow path at the intersection (6) of the dispersed phase and the continuous phase may be used. As shown, the continuous phase (10) intersects with two or more disperse phases (15), and the disperse phase is sheared by the shearing force between the continuous phase and the wall of the inner wall of the flow path at the intersection (6). A method of generating fine particles (17) may be used, and as shown in FIG. 9, the dispersed phase (15) is linearly formed from one side of the flow path (16) and the continuous phase (10) is formed from the other side. Is introduced by the shear force of the continuous phase and the inner wall of the flow path at the intersection (6) of the continuous phase and the dispersed phase. To produce that in fine particles to be sheared phase (17), or in a manner to be discharged to the discharge passage for any direction of one or more than intersections (6). By doing in this way, microparticles can be generated more efficiently. In the case of the method of FIG. 9, the microparticles generated by intersecting the fluid containing the generated microparticles again can be collected.

  Further, as shown in FIGS. 10 to 13, a dispersed phase introduction channel (5) for introducing a plurality of dispersed phases (15) and a continuous phase introduction channel (3) for introducing a plurality of continuous phases (10) are provided. By providing, a disperse phase or a continuous phase can be made into a laminar flow of plural fluids, a mixed liquid, or a suspension (emulsion).

  FIG. 10 shows a case where the dispersed phase is a two-phase two-phase laminar flow, and the dispersed phase is sheared with a continuous phase, whereby fine particles having a two-phase structure can be formed. In this case, the dispersed phase is not limited to a two-liquid two-phase laminar flow, and may be two or more. For example, as shown in FIG. 13, the dispersed phase may be a four-phase laminar flow composed of four liquids. In this case, the fine particles can have a four-layer structure. Further, as shown in FIG. 11, the dispersed phase may be a reaction liquid obtained by reacting two liquids. In this case, it is possible to generate microparticles composed of reaction products generated in the microchannel. Needless to say, the reaction fluid may be two or more liquids. Further, as shown in FIG. 12, a reaction liquid obtained by reacting two liquids in a dispersed phase and a continuous phase may be used. In this case, it is possible to generate fine particles by shearing the dispersed phase composed of the reaction product generated in the microchannel by the continuous layer formed from the reaction product generated in the microchannel. In this case as well, it goes without saying that the fluid to be reacted in the dispersed phase and the continuous phase may be two or more liquids.

  As described above, by adopting the embodiments as shown in FIGS. 10 to 13, it is possible to form a microparticle having a multilayer structure or a microparticle containing various kinds of microparticles, and generate a composite microcapsule or a multiple microcapsule. can do. Note that the continuous phase, the dispersed phase, or both may contain fine powder.

  In the present invention, when the microparticles generated at the intersection of the channels are microdroplets and the microdroplets are cured, they may be cured in the channel and / or outside the channel. Furthermore, in order to make the particle size of the hardened microparticles uniform, after the microdroplet passes through the discharge channel and exits the discharge unit, the microchannel structure is discharged from the discharge unit to the outside of the microchannel structure. It may be continuously cured in the flow path provided in the. Furthermore, in order to make the particle size of the hardened microparticles more uniform, it is more preferable that the microparticles are cured in the discharge channel in the microchannel structure immediately after the microdroplet is generated at the intersection of the channels. .

  One of the means for curing the microdroplets in the present invention is to cure by irradiating the microdroplets with light. In this case, the light is cured from a relatively large number of materials. Since it can be selected, ultraviolet rays are preferable. The light irradiation (21) may be performed after the fine droplets are discharged from the discharge port (8) of the microchannel structure (19) as shown in FIG. In order to make the particle size of the particles more uniform, as shown in FIG. 15, light irradiation (21) is performed immediately after the microdroplet is generated at the intersection (6) of the channel, and the microchannel structure ( It is more preferable to harden in the discharge flow path (7) in 19). However, when light irradiation is performed in the discharge channel in the microchannel structure, before the microdroplet is generated, the dispersed phase is not irradiated and cured before the microdroplet is generated. As shown in FIG. 15, the portion of the discharge channel and the portion of the discharge channel that cures the micro-droplet by irradiating light is irradiated with the light irradiation spot (20) only at the necessary portion of the micro-channel structure. Thus, it is necessary to install a mask (22).

  Another means for curing the microdroplets in the present invention is a method for producing microparticles using a means for curing the microdroplets by heating. As shown in FIG. 16, heating may be performed by a heater (28) or the like after a micro droplet comes out of the micro channel structure from the outlet (8) of the micro channel structure (19). In order to make the particle size of the microparticles more uniform, as shown in FIG. 17, the microchannel is heated by a heater (28) or the like immediately after the microdroplet is generated at the intersection (6) of the channel. It is more preferable to harden in the discharge channel (7) in the structure. However, when heating is performed in the discharge channel in the microchannel structure, the discharge flow before the microdroplet is generated so that the dispersed phase is not heated and hardened before the microdroplet is generated. The part of the channel and the part of the discharge channel that cures the micro droplets by heating must be thermally insulated by a known heat insulation method such as embedding a heat insulating material in the micro channel structure. is there.

  In the present invention, when the microdroplet is cured by light irradiation or heating, the entire microdroplet may be cured. It may be cured to such an extent that the droplets do not coalesce. In this case, semi-cured microparticles are collected with a beaker or the like, and completely cured again by light irradiation or heating, whereby uniform microparticles with a good particle size dispersion can be obtained.

  In this way, if the microparticles generated at the intersection of the flow channels are microdroplets, they are collected by a beaker etc. outside the flow channel, and when the microdroplets are cured by cross-linking polymerization, the microdroplets are collected. Since the shape of the microparticles collapses or coalesces between the microparticles before curing, the particle size dispersion of the cured microparticles is not increased, and the particle size dispersion is good. Can obtain uniform fine particles. Moreover, it becomes easy to separate from the medium by curing the fine droplets.

  In the method for producing microparticles of the present invention, examples of the use of microparticles include packing materials for high-performance liquid chromatography columns, pressure measurement films, carbonless (pressure-sensitive copying) paper, toners, thermal expansion agents, thermal media, preparations. Light glass, gap agent (spacer), thermochromic (thermosensitive liquid crystal, thermosensitive dye), magnetophoresis capsule, pesticide, artificial feed, artificial seed, fragrance, massage cream, lipstick, vitamins capsule, activated carbon, enzyme-containing capsule And microcapsules and gels such as DDS (drug delivery system).

  Moreover, the microchannel structure of the present invention is generated by the inlet and the inlet channel for introducing the dispersed phase, the inlet and the inlet channel for introducing the continuous phase, and the dispersed phase and the continuous phase. A microchannel structure comprising a channel having a discharge channel and a discharge port for discharging microparticles, wherein the continuous phase is dispersed with respect to the dispersed phase flowing in the microchannel. Discharge from the continuous phase supply port in a direction that intersects the phase flow at an arbitrary angle, generates fine particles from the dispersed phase by the shear force of the continuous phase and the wall surface in the flow path, and controls the diameter of the fine particles This is a microchannel structure characterized in that Needless to say, the microchannel structure of the present invention is not limited to the examples of FIGS. 6 to 17 and can be arbitrarily changed without departing from the gist of the present invention. Here, the introduction port for introducing the dispersed phase means an opening for introducing the dispersed phase, and a mechanism for continuously introducing the dispersed phase by providing an appropriate attachment at the introduction port. Similarly, the introduction port for introducing the continuous phase also means an opening for introducing the continuous phase, and further, as a mechanism for continuously introducing the continuous phase with an appropriate attachment at the introduction port. Good.

  The dispersed phase introduction flow path for introducing the dispersed phase is a microchannel communicating with the introduction port, and the dispersed phase is introduced and fed along the introduction flow path. The shape of the introduction channel affects the shape and particle size of the fine particles, but the channel width is 500 μm or less, preferably 300 μm or less. Moreover, what is necessary is just to become a shape which cross | intersects a continuous phase introduction flow path and a discharge flow path at arbitrary angles. In addition, the continuous phase introduction flow path for introducing the continuous phase communicates with the continuous phase introduction port, and the continuous phase is introduced and fed along the introduction flow path. The shape of the introduction channel has an effect on controlling the shape and particle size of the microparticles, but the channel is not particularly limited to the microchannel, and the channel width of the continuous phase introduction channel corresponds to the microchannel. The width may not be a width to be used, or may be a width corresponding to a microchannel. The discharge channel is substantially continuous with the continuous phase introduction channel, and the discharge channel exists as an extension of the continuous phase introduction channel. Therefore, the discharge flow path substantially continuous with the continuous phase introduction flow path is not limited to the microchannel, and the discharge width of the discharge flow path may not be a width corresponding to the microchannel. It may be a width corresponding to. Rather, in order to improve the particle size dispersion of the microparticles, which is the object of the present invention, it is preferable that the continuous phase introduction flow path and the discharge flow path are not microchannels. preferable. Further, the depth and / or width of the discharge channel from the intersection where the dispersed phase and the continuous phase intersect to the discharge port are larger than the depth and / or width of the channel through which the dispersed phase flows, and the depth. More preferably, the position where the width becomes larger is the position before the generated microdroplet is decomposed into the first type quasi-microdroplet smaller than the microdroplet.

  The reason for this will be described in more detail below with reference to the drawings.

  As a result of intensive studies by the present inventors, the dispersed phase is discharged from the dispersed phase supply port in the direction intersecting the continuous phase flow with respect to the continuous phase flowing in the microchannel, and the dispersed phase is minutely separated from the dispersed phase by the shear force of the continuous phase. When a droplet is generated, the microdroplet continues to flow through the continuous phase of the microchannel. In this case, the phenomenon described below occurs depending on whether the particle size of the generated microdroplets is larger or smaller than the width or depth of the continuous phase that is a microchannel.

  First, as a first case, as shown in FIG. 3, the particle size of the generated microdroplet (34) is the width or depth of the continuous phase introduction channel (3) and the discharge channel (7) which are microchannels. If it is larger than the thickness, the shear stress resulting from the difference in interfacial tension between the microdroplet and the continuous phase (10) surrounding the microdroplet and the shear stress of the inner wall (25) of the flow channel act on the microdroplet, The main rear part of the droplet gradually collapses as shown in FIG. The collapsed portion is decomposed from the microdroplet, and the first type quasi-microdroplet (12) which is a microdroplet further smaller than the average particle size having a particle size of about 20 to 30% or less of the average particle size; Become.

  Next, as a second case, the particle diameter of the generated micro droplet (34) is smaller than the width or depth of the continuous phase introduction channel (3) and the discharge channel (7) which are micro channels. In this case, the shear stress resulting from the interfacial tension difference between the microdroplet and the continuous phase (10) surrounding the microdroplet acts on the microdroplet, and the rear part of the microdroplet is mainly shown in FIG. 4 as in the first case. It gradually collapses as shown. The collapsed portion is decomposed from the microdroplet, and the first type quasi-microdroplet (12) which is a microdroplet further smaller than the average particle size having a particle size of about 20 to 30% or less of the average particle size; Become. However, in the case of the second case, since the shear stress of the inner wall (25) of the flow path does not work compared to the case of the first case, the position (14) where the rear part of the micro droplet starts to collapse is the disperse phase. The position is further away from the position where the continuous phases intersect.

In either case, the microdroplet decomposes due to the shear stress generated from the interfacial tension between the microdroplet and the continuous phase surrounding the microdroplet and the shear stress of the inner wall of the flow path, thereby reducing the first type The particle size dispersion degree of the fine droplets generated by the generation of the fine droplets is very poor at 20 to 30% or more. Therefore, in order to improve the particle size dispersion degree of the generated microdroplets, the shear stress generated from the interfacial tension between the generated microdroplets and the continuous phase surrounding the microdroplets and the inner wall of the flow path By preventing shear stress from occurring, the microdroplet may be discharged from the microchannel structure together with the continuous phase from the outlet without being decomposed.
Therefore, the microchannel structure of the present invention discharges the continuous phase from the continuous phase supply port in a direction intersecting the flow of the dispersed phase at an arbitrary angle with respect to the dispersed phase flowing in the microchannel, In order to introduce the disperse phase, the microchannel structure is characterized in that microparticles are generated from the disperse phase by the shearing force of the wall surface in the channel and the diameter of the microparticles is controlled. Since the dispersed phase introduction flow path is a microchannel communicating with the introduction port, it is possible to generate microparticles having an average particle size of several hundred μm or less, and the generated microdroplets are discharged from the microchannel structure. By not limiting the discharge channel that is carried along with the continuous phase to the discharge port and the continuous phase introduction channel that is substantially continuous with the discharge channel to the microchannel, The boundary with the surrounding continuous phase Shear stress of the inner wall of the shear stress and the flow path resulting from the tension has become possible to prevent the occurrence. Here, the continuous-phase introduction flow path and the discharge flow path are not limited to microchannels, and as shown in FIG. 19 which is a cross-sectional view taken along the line BB ′ in FIGS. ) And the channel depth (40) may be microchannels as long as they are sufficiently larger than the average particle size of the generated microdroplets (34). However, when the average particle size of the fine droplets is defined as several hundred μm or less, in order to improve the particle size dispersion degree of the fine particles, which is the object of the present invention, rather, C− in FIG. 20 and FIG. As shown in FIG. 21 which is a C ′ sectional view and FIG. 22 which is a DD ′ sectional view, it is preferable that the continuous phase introduction flow path (3) and the discharge flow path (7) are not microchannels. More preferably, the microchannel is not used. Furthermore, as shown in FIG. 24 which is a cross-sectional view taken along the line EE ′ in FIG. 23 and FIG. 23 and FIG. 25 which is a cross-sectional view taken along the line FF ′, the intersecting portion where the dispersed phase (15) and the continuous phase (10) intersect. It is preferable that the depth and / or width of the discharge channel (7) from (6) to the discharge port (8) is larger than the depth and / or width of the channel through which the dispersed phase flows. Further, FIG. 26 and FIG. 27 show the generation of microparticles when the depth and / or width of the discharge channel increases from the middle. In FIG. 26, the position where the depth and / or width of the discharge channel increases is farther away from the intersection where the dispersed phase and the continuous phase intersect than the position where the generated microdroplet starts to collapse. FIG. 27 is a conceptual diagram showing the generation of microparticles in a position closer to the intersection where the dispersed phase and the continuous phase intersect. In addition, the auxiliary line (broken line) in FIG.26 and FIG.27 respond | corresponds to the positional relationship of both figures. Accordingly, as shown in FIG. 26 and FIG. 27, the position (24) where the depth and / or width of the discharge channel (7) increases, the generated microdroplet (34) collapses at the rear of the microdroplet. A form that is closer to the intersection (6) where the dispersed phase (15) and the continuous phase (10) intersect is more preferable than the starting position (14). Therefore, it is possible to prevent the shear stress generated from the interfacial tension with the continuous phase (10) surrounding the micro droplet and the inner wall (25) of the flow channel from being generated, and the micro droplet is decomposed in the discharge flow channel. Therefore, it is possible to discharge the micro droplet from the micro flow channel structure together with the continuous phase from the discharge port. In addition, it goes without saying that the position at which the fine droplets are decomposed differs depending on the magnitude of the difference in interfacial tension between the dispersed phase and the continuous phase. Generally, the greater the difference in interfacial tension between the dispersed phase and the continuous phase, the greater the difference. The micro droplet is decomposed at a position closer to the intersection where the micro droplet is generated.

  By using the microchannel structure as described above, it is possible to suppress the generation of the first type quasi-microdroplets having an average particle size of about 20 to 30% or less, and to improve the particle size dispersion to less than 10%. It became possible to let you.

  In addition, the discharge flow path may be two or more discharge flow paths separated from the intersection at an arbitrary angle. Further, the discharge port means an opening for discharging the generated fine particles, and a mechanism for continuously discharging the phase containing the generated fine particles with an appropriate attachment provided at the discharge port. .

  Further, in the microchannel structure of the present invention, the width of the discharge channel is narrow at a part of the discharge channel from the intersection where the dispersed phase and the continuous phase intersect to the discharge port, and the discharge channel is discharged. The part where the width of the flow path is narrow is at or near the intersection of the dispersed phase and the continuous phase flowing in the microchannel, and / or the part where the width of the discharge flow path is narrow is the microchannel. It is preferably on the introduction flow path side of the dispersed phase at the intersection of the dispersed phase flowing through and the continuous phase. Furthermore, it is preferable that one or more protrusions are formed from the bottom surface, top surface, and / or side surface of the flow channel in the vicinity of the intersection between the dispersed phase and the continuous phase flowing in the microchannel.

  Here, FIGS. 28 to 36 show an example in which one or more protrusions are formed from any one or two or more of the bottom, top, and side surfaces of the flow path.

  FIG. 28 is a conceptual diagram showing an example of a microchannel structure in which one or more protrusions are formed from any one or two or more of the bottom, top, and side surfaces of the channel. Examples of an enlarged portion of the intersection (6) between the continuous phase introduction flow path and the dispersed phase introduction flow path in FIG. 28 and its cross-sectional view are shown in FIGS. FIG. 29 is a conceptual diagram showing an example of a microchannel structure in which one or more protrusions are formed from the bottom surface of the channel. FIG. 30 is a G-G ′ cross-sectional view of the flow path in FIG. 29. FIG. 31 is a conceptual diagram showing an example of a micro-channel structure in which one or more protrusions are formed from the upper surface of the channel. 32 is a cross-sectional view taken along the line H-H ′ in FIG. 31. FIG. 33 is a conceptual diagram showing an example of a micro-channel structure in which one or more protrusions are formed from the bottom and side surfaces of the channel. 34 is a cross-sectional view of the flow path in FIG. 33 taken along the line J-J ′. FIG. 35 is a conceptual diagram showing an example of a micro-channel structure in which one or more protrusions are formed from the bottom, top, and side surfaces of the channel. FIG. 36 is a K-K ′ sectional view of the flow path in FIG. 35.

  By doing in this way, in addition to the liquid feeding pressure of the continuous phase, it is possible to shear the dispersed phase more easily due to the increase in internal pressure due to the narrow inside of the flow path, which occurs when shearing The tailing (31) of the microdroplet (34) as shown in FIGS. 3 and 4 can be suppressed, and the microdroplet (34) without the tailing can be generated as shown in FIG. It becomes. As shown in FIG. 2C, tailing means that when the dispersed phase (15) is broken by the shear of the continuous phase (10), the dispersed phase is broken due to the difference in interfacial tension between the dispersed phase and the continuous phase. It refers to a long and thin linear dispersed phase surrounded by a continuous phase and continuing from the rear of the micro droplet generated when trying to do so. As shown in FIGS. 3 and 4, the tailing of the microdroplet is a second-type quasi-microdroplet (less than 10 μm) because the tail portion is broken when the dispersed phase is sheared to become a droplet. 13) occurs, which is one of the factors that deteriorate the particle size dispersion degree. That is, by using the microchannel structure having the channel structure as described above, the tailing of the microdroplets is suppressed, so that the particle size dispersion degree of the microparticles which is the object of the present invention is 10%. For the first time, it is possible to provide a microchannel structure that generates microparticles having a uniform particle size of less than 1 and a microparticle manufacturing method using the microchannel structure.

  Furthermore, in the microchannel structure according to the present invention, the dispersed phase introduction channel for introducing the dispersed phase and the continuous phase introduction channel for introducing the continuous phase intersect at an arbitrary angle, and these introductions It is preferable that the flow path be connected to the discharge flow path at an arbitrary angle. By setting the angle at which the two introduction channels intersect to be an arbitrary angle, it is possible to control the fine particles generated at the intersection to a desired particle size. What is necessary is just to determine suitably about the setting of a crossing angle according to the particle size of the target fine particle.

In addition, the microchannel structure of the present invention can industrially generate a large amount of microparticles by arranging a plurality of microchannels planarly or three-dimensionally in the microchannel structure. FIG. 52, which is a cross-sectional view taken along line OO ′ in FIG. 51 and FIG. 51, and FIG. 53, which is a cross-sectional view taken along line PP ′, show an example of the above embodiment. This is an example in which a substrate (1) having a channel (35) is overlapped, and a common channel (29) is formed through the substrate. This form is effective when stacking substrates and stacking a large number of three-dimensional microchannels. The present invention is not limited to this embodiment, and a plurality of flow paths may be arranged in any arrangement on a single substrate, and can be arbitrarily changed without departing from the gist of the invention. Needless to say, in various forms of the present invention, the fluid is generally introduced into the fluid inlet using a liquid feed pump such as a syringe pump, but the fluid is discharged from the outlet of the passage arranged in the passage. The fluid may be collected, returned to the liquid feed pump, and fed again. By doing in this way, the continuous phase and / or disperse phase to introduce can be used without waste.

  The microchannel structure according to the present invention has the structure and performance described above, but includes an introduction part and an introduction channel for introducing a dispersed phase and a continuous phase, and an intersection where the introduction channel intersects. The micro flow channel structure having a discharge flow channel and a discharge port for discharging the liquid covers the substrate having the flow channel formed on at least one surface and the substrate surface on which the flow channel is formed. A cover body in which small holes for communicating the flow channel and the outside of the micro flow channel structure are arranged at a predetermined position of the flow channel may be laminated and integrated. As a result, the fluid can be introduced from the outside of the microchannel structure into the channel and discharged again to the outside of the microchannel structure, and the fluid can be stably flowed even if the amount of fluid is small. It is possible to pass through the road. The fluid can be fed by mechanical means such as a syringe pump or a micro pump.

  As the material of the substrate and the cover body on which the flow path is formed, it is desirable that the flow path can be formed, has excellent chemical resistance, and has an appropriate rigidity. For example, glass, quartz, ceramic, silicon, or metal or resin may be used. The size and shape of the substrate and cover body are not particularly limited, but the thickness is preferably about several mm or less. The small hole arranged in the cover body communicates the flow path and the outside of the micro flow path structure and has a diameter of, for example, about several hundred μm to several mm when used as a fluid inlet or outlet. It is desirable. The small holes in the cover body can be processed chemically, mechanically, or by various means such as laser irradiation or ion etching.

  In the microchannel structure of the present invention, the substrate on which the channel is formed and the cover body can be laminated and integrated by means such as heat bonding or bonding using an adhesive such as a thermosetting resin.

  The microchannel structure according to the present invention includes an introduction port for introducing a dispersed phase and a dispersed phase introduction channel, an introduction port for introducing a continuous phase and a continuous phase introduction channel, and a dispersed phase and a continuous phase. A microchannel structure comprising a channel having a discharge channel and a discharge port for discharging the generated microparticles, wherein the continuous phase is different from the dispersed phase flowing in the microchannel. Is discharged from the continuous phase supply port in a direction intersecting with the flow of the dispersed phase at an arbitrary angle, and fine particles are generated from the dispersed phase by the shear force of the continuous phase and the wall surface in the flow path. And a depth of the discharge channel from the intersection where the disperse phase flowing through the microchannel intersects with the continuous phase intersects the discharge port and / or Width is the depth of the flow path through which the dispersed phase flows and Or a microchannel structure characterized by being larger than the width, and the depth and / or width of the discharge channel from the intersection where the dispersed phase and the continuous phase intersect to the discharge port are The position where the depth and / or width of the flowing channel is larger than the depth of the flow path is a position before the generated micro droplet is decomposed into the first type quasi-micro droplet smaller than the micro droplet. This is a microchannel structure. By using such a microchannel structure, it is possible to prevent the generated microdroplet from generating shear stress resulting from the interfacial tension between the continuous phase surrounding the microdroplet and the inner wall of the channel. It is possible to discharge the microdroplet together with the continuous phase from the outlet without decomposing the microdroplet in the discharge channel, and the first type quasi-microdroplet of about 20 to 30% or less of the average particle diameter. Generation can be suppressed, the degree of particle size dispersion can be improved to less than 10%, and fine particles with a uniform particle size can be generated.

  Further, in the microchannel structure of the present invention, the discharge channel has a width at a part of the discharge channel from the intersection where the dispersed phase flowing in the microchannel intersects with the continuous phase intersects to the discharge port. A micro-channel structure characterized in that the portion where the width of the discharge channel is narrow is in the vicinity of or near the intersection where the dispersed phase flowing through the micro-channel and the continuous phase intersect And the portion where the width of the discharge channel is narrow is on the disperse phase introduction channel side of the intersecting portion where the disperse phase flowing in the microchannel intersects the continuous phase. In the vicinity of the intersection where the dispersed phase flowing in the microchannel intersects with the continuous phase intersecting, one or more protrusions are formed from the bottom, top and / or side surfaces of the channel. That A fine channel device according to symptoms. By making such a microchannel structure, it becomes possible to generate microdroplets without tailing, and when the dispersed phase is sheared into droplets, the tail portion is separated and becomes 10 μm. It is possible to suppress the generation of less than the second type quasi-microdroplets, and it is possible to generate microparticles having a very uniform particle size with a particle size dispersion degree of less than 10%. .

  The method for producing microparticles of the present invention is a microparticle production method for producing microparticles using a microchannel structure having any one of the forms described above, and is further used for introducing a dispersed phase. A method for producing microparticles, characterized by controlling the particle size of the microparticles generated by changing the angle at which the flow channel and the introduction flow channel for introducing the continuous phase intersect. Thus, it is possible to provide a method for freely controlling the average particle size and producing fine particles having a very uniform average particle size with a particle size dispersion of less than 10%.

  Hereinafter, examples of the present invention will be described, and the embodiments of the invention will be described in more detail. It is needless to say that the present invention is not limited to the following examples and can be arbitrarily changed without departing from the gist of the present invention.

  The microchannels in the first embodiment of the present invention are shown in FIGS. 37 and 38, which are L-L 'cross-sectional views in FIG. 37 and FIG. On a Pyrex (registered trademark) glass of 70 mm × 20 mm × 1 t (thickness), a dispersed phase corresponding to a continuous phase introduction channel (3) having a width of 600 μm and a depth of 100 μm, and a microchannel having a width of 200 μm and a depth of 100 μm An introduction channel (4) and a discharge channel (7) having a width of 600 μm, a depth of 100 μm, and a length of 30 mm, and an angle of 44 ° between the continuous phase introduction channel (3) and the dispersed phase introduction channel (5) A substrate (1) on which one Y-shaped channel having an intersecting portion intersecting with each other was formed. Therefore, in this embodiment, the width of the continuous phase introduction channel and the discharge channel is larger than the width of the micro channel defined in the present invention, that is, 500 μm, and the dispersed phase introduction channel is a micro channel. It is an example.

  As shown in FIG. 40, the microchannel structure having the channel is formed on one surface of a glass substrate having a thickness of 1 mm and a size of 70 mm × 20 mm by a general photolithography and wet etching. A small hole having a diameter of 0.6 mm is formed in advance on the surface of the substrate (1) having the flow path at positions corresponding to the inlet (11) and the outlet (8) of the flow path using mechanical processing means. A provided glass cover body (30) having a thickness of 1 mm and a size of 70 mm × 20 mm was thermally bonded.

  Next, the microdroplet manufacturing method of the present embodiment will be described. As shown in FIG. 41, the microchannel structure (19) is held by a holder (23) or the like so that liquid can be fed, and the Teflon (registered trademark) tube (27) and fillet joint (36) are held by the holder. Secure to. The other end of the Teflon tube is connected to a microsyringe (38). Thus, liquid can be fed to the microchannel structure.

  Next, a mixed solution of divinylbenzene and butyl acetate is injected into the dispersed phase for generating microdroplets, and a 3% aqueous solution of polyvinyl alcohol is injected into each microsyringe as the continuous phase, and the solution is fed by the microsyringe pump (37). went. The liquid feeding speed is 3 μl / min for both the dispersed phase and the continuous phase. In the state where both the liquid feeding speeds were stable, the generation of microdroplets as shown in FIG. 42 was observed at the intersection where the dispersed phase and continuous phase of the microchannel structure intersect. When the generated fine droplets are observed, as shown in FIG. 43, the average particle size is 80 μm, the CV value (%) indicating the particle size dispersion is 8.1%, and the particle size dispersion is less than 10%, which is extremely uniform. Fine droplets (34). In Example 1, approximately 30% or less of the average particle size of 80 μm, that is, substantially no first-type quasi-microdroplets having a particle size of about 25 μm or less was observed. However, type 2 quasi-microdroplets with a particle size of less than 10 μm were observed. As shown in Example 1, the width of the continuous phase introduction channel and the discharge channel is larger than the width of the micro channel defined in the present invention, that is, 500 μm, and the dispersed phase introduction channel is a micro channel. As a result, the degree of dispersion is higher than that of the comparative example described later. Therefore, the shear stress generated from the interfacial tension between the generated microdroplet and the continuous phase surrounding the microdroplet and the shear stress of the inner wall of the flow path are The microdroplets can be discharged from the discharge port together with the continuous phase without being decomposed in the discharge flow path, and the average particle diameter is about 20 to 30% or less. It was possible to suppress the generation of one kind of fine droplets and to improve the particle size dispersion to less than 10%.

  FIG. 45 shows a microchannel according to the second embodiment of the present invention. The microchannel is a Pyrex (registered trademark) glass having a size of 70 mm × 40 mm × 1 t (thickness), a continuous phase introduction channel (3) corresponding to the microchannel, a dispersed phase introduction channel (5), and a discharge channel. Each of the widths of (7) is 200 μm and the depth is 300 μm, and a Y-shaped channel having an intersection (6) where the continuous phase introduction channel and the dispersed phase introduction channel intersect at an angle of 44 °. Formed. Therefore, in this embodiment, the width of the continuous phase introduction channel, the dispersed phase introduction channel, and the discharge channel is set to the width of the micro channel, which is about twice or more than the particle size of the micro droplet that generates the depth. This is an example when it is made sufficiently large.

  The micro-channel is formed by general photolithography and dry etching, and corresponds to the inlet (11) and the outlet (8) of the channel on the surface of the glass substrate on which the channel is formed. A glass cover body having a thickness of 1 mm and a thickness of 70 mm × 20 mm provided with a small hole having a diameter of 0.6 mm in advance at a position using mechanical processing means was manufactured by thermal bonding in the same manner as in Example 1.

  Next, the microchannel structure is held by a holder, and a mixed solution of monomer (styrene), divinylbenzene, butyl acetate and benzoyl peroxide is used as a dispersed phase for generating microdroplets in the same manner as in Example 1. Was injected into a microsyringe as a continuous phase, and the solution was fed with a microsyringe pump to produce fine droplets. The liquid feeding speed is 1 μl / min for the dispersed phase and 15 μl / min for the continuous phase. Formation of microdroplets was observed at the intersection where the dispersed phase and continuous phase of the microchannel structure intersect, with both flow rates stabilized. Observing the generated microdroplets, the average particle size is 98.3 μm, the CV value (%) indicating the degree of dispersion of the particle size is 8.5%, and the extremely uniform micro liquid with a particle size dispersion of less than 10%. It was a drop. In Example 2, substantially no first-type quasi-microdroplets having an average particle size of 98.3 μm or less, ie, about 30% or less, that is, a particle size of about 30 μm or less were not observed. However, type 2 quasi-microdroplets with a particle size of less than 10 μm were observed.

  As shown in the present Example 2, even if the width of the continuous phase introduction channel, the dispersed phase introduction channel, and the discharge channel is the micro channel size defined in the present invention, the depth of the micro channel is reduced. By making it sufficiently larger than the particle size of the generated microdroplets (for example, about twice or more), the degree of dispersion is improved compared to the comparative example described later. The shear stress generated from the interfacial tension with the surrounding continuous phase and the shear stress of the inner wall of the flow path can be prevented, and the micro liquid droplets can be removed from the discharge port without decomposition in the discharge flow path. So that the generation of the first type quasi-microdroplets of about 20 to 30% or less of the average particle size can be suppressed, and the degree of particle size dispersion can be improved to less than 10%. became.

  FIG. 48 shows a microchannel according to the third embodiment of the present invention. The microchannels are on Pyrex (registered trademark) glass of 70 mm × 40 mm × 1 t (thickness), and the widths of the continuous phase introduction channel (3) and the dispersed phase introduction channel (5) corresponding to the microchannels are any. Further, a Y-shaped channel having an intersection (6) where the continuous phase introduction channel and the dispersed phase introduction channel intersect at an angle of 44 ° was formed with a depth of 200 μm and a depth of 100 μm. The discharge channel is a micro channel having a width of 200 μm and a depth of 100 μm from the intersection of the continuous phase introduction channel and the dispersed phase introduction channel to a position of 3 mm, and thereafter, a channel having a width of 600 μm and a depth of 250 μm. It was. Therefore, in this embodiment, the continuous phase introduction flow path and the dispersed phase introduction flow path are micro flow paths, and the middle of the discharge flow path is the micro flow path, and the generated micro liquid droplets are surrounded by the continuous phase. Shear stress caused by interfacial tension and shear stress of the inner wall of the flow path are generated, and the width and depth of the discharge flow path are generated before the micro liquid droplets are decomposed in the discharge flow path. This is an example in the case where it is sufficiently large.

  The channel is formed by general photolithography and wet etching, and a diameter of 0.6 mm is previously provided at a position corresponding to the inlet (11) of the channel on the surface of the glass substrate on which the channel is formed. In the same manner as in Example 1, a glass cover body having a thickness of 1 mm and a thickness of 70 mm × 20 mm provided in advance using a mechanical processing means is provided in a position corresponding to the discharge port (8). I made it.

  Next, the microchannel structure is held by a holder, and a mixed solution of monomer (styrene), divinylbenzene, butyl acetate and benzoyl peroxide is used as a dispersed phase for generating microdroplets in the same manner as in Example 1. Was injected into a microsyringe as a continuous phase, and the solution was fed with a microsyringe pump to produce fine droplets. The liquid feeding speed is 6 μl / min for the dispersed phase and 15 μl / min for the continuous phase. Formation of microdroplets was observed at the intersection where the dispersed phase and continuous phase of the microchannel structure intersect, with both flow rates stabilized. When the generated microdroplets are observed, the average particle size is 120.8 μm, the CV value (%) indicating the degree of dispersion of the particle size is 8.3%, and the extremely uniform minute liquid having a particle size dispersion of less than 10%. It was a drop. In Example 3, substantially no first-type quasi-microdroplets having an average particle diameter of 120.8 μm or less, that is, approximately 30% or less, that is, a particle diameter of approximately 35 μm or less were not observed. However, type 2 quasi-microdroplets with a particle size of less than 10 μm were observed.

  As shown in the third embodiment, even if the width of the continuous phase introduction channel, the dispersed phase introduction channel, and the discharge channel is the micro channel defined in the present invention, The width and depth of the discharge channel from the middle of the discharge channel before the microdroplet breaks down in the discharge channel due to the shear stress resulting from the interfacial tension with the continuous phase surrounding the droplet and the shear stress of the inner wall of the channel By making the size sufficiently large (for example, about twice or more), the degree of dispersion is improved compared to the comparative example described later. The shear stress generated by the interfacial tension with the surrounding continuous phase and the shear stress of the inner wall of the flow path work, so that the microdroplets can be discharged together with the continuous phase from the outlet before the microdroplets are decomposed. Suppresses the generation of the first type quasi-microdroplets with a diameter of 20-30% or less. Can be, it becomes the degree of particle diameter distribution to be able to improve to less than 10%.

  FIG. 47, which is an enlarged view of the vicinity of the intersection in FIGS. 46 and 46, shows the micro flow path in the fourth embodiment of the present invention. The microchannels are on Pyrex (registered trademark) glass of 70 mm × 40 mm × 1 t (thickness), and the widths of the continuous phase introduction channel (3) and the dispersed phase introduction channel (5) corresponding to the microchannels are any. Further, a Y-shaped channel having an intersection (6) where the continuous phase introduction channel and the dispersed phase introduction channel intersect at an angle of 44 ° was formed with a depth of 200 μm and a depth of 100 μm. The discharge channel (7) is a micro channel having a width of 200 μm and a depth of 100 μm from the intersection of the continuous phase introduction channel and the dispersed phase introduction channel to a position of 3 mm, and after that, a width of 600 μm and a depth of 250 μm. It was set as the flow path. Further, in the discharge channel immediately after the intersection of the continuous phase introduction channel and the dispersed phase introduction channel, the wall surface of the discharge channel on the dispersed phase introduction channel side has a channel width of 200 μm as shown in FIG. A protrusion protruding to the inside of about 50 μm at the maximum was formed. Therefore, in this embodiment, the continuous phase introduction flow path and the dispersed phase introduction flow path are micro flow paths, and the micro flow path is formed halfway through the discharge flow path. Shear stress caused by interfacial tension and shear stress of the inner wall of the flow path are generated, and the width and depth of the discharge flow path are generated before the micro liquid droplets are decomposed in the discharge flow path. This is an example in which the protrusion is formed on the wall surface of the discharge channel on the side of the dispersed phase introduction channel in the discharge channel immediately after the intersection of the continuous phase introduction channel and the dispersed phase introduction channel. .

  The channel is formed by general photolithography and wet etching, and a small hole having a diameter of 0.6 mm is previously formed in the inlet (11) of the channel on the surface of the glass substrate on which the channel is formed. A glass cover body having a thickness of 1 mm and a thickness of 70 mm × 20 mm provided in advance using a mechanical processing means is thermally bonded in the same manner as in Example 1 to a position corresponding to the discharge port (8). did.

  Next, the microchannel structure is held by a holder, and a mixed solution of monomer (styrene), divinylbenzene, butyl acetate and benzoyl peroxide is used as a dispersed phase for generating microdroplets in the same manner as in Example 1. Was injected into a microsyringe as a continuous phase, and the solution was fed with a microsyringe pump to produce fine droplets. The liquid feeding speed is 6 μl / min for the dispersed phase and 15 μl / min for the continuous phase. Formation of microdroplets was observed at the intersection where the dispersed phase and continuous phase of the microchannel structure intersect, with both flow rates stabilized. When the generated microdroplets are observed, as shown in FIG. 47, the phenomenon of tailing (31) that occurs at the moment when the microdroplets (34) shown in FIGS. 3 and 4 are formed by shearing is substantially observed. Was not. The produced microdroplets have an average particle size of 118.2 μm, a CV value (%) indicating the degree of dispersion of the particle size of 4.8%, and an extremely uniform microfluid having a particle size dispersion of less than 5%. It was a drop. In Example 4, substantially no first-type quasi-microdroplets having an average particle size of 118.2 μm or less, that is, about 30% or less, that is, a particle size of about 35 μm or less were not observed. Furthermore, substantially no second-type quasi-microdroplets having a particle size of less than 10 μm were observed.

  As shown in the fourth embodiment, the continuous phase introduction flow path and the dispersed phase introduction flow path are micro flow paths, and the micro flow paths are formed halfway along the discharge flow path, and the generated micro liquid droplets are continuously surrounded by the micro liquid droplets. Compared to the microdroplet that generates the width and depth of the discharge channel before the microdroplet breaks down in the discharge channel due to the shear stress caused by the interfacial tension with the phase and the shear stress of the inner wall of the channel A protrusion is formed on the wall of the discharge channel on the dispersed phase introduction channel side in the discharge channel immediately after the intersection of the continuous phase introduction channel and the dispersed phase introduction channel. As a result, the tailing of the microdroplet that occurs when the microdroplet is sheared by the shearing of the continuous phase and the inner wall of the flow path can be suppressed. Since the degree of dispersion is much better than The shear stress generated from the interfacial tension with the surrounding continuous phase and the shear stress of the inner wall of the channel work, and before the micro droplet breaks down, the micro droplet is discharged together with the continuous phase, and the continuous phase introduction channel By forming protrusions on the wall of the discharge channel on the side of the dispersed phase introduction channel at the discharge channel immediately after the intersection of the dispersed phase introduction channel and the dispersed phase introduction channel, microdroplets are sheared by the shear of the continuous phase and the inner wall of the channel Since the tailing of the micro droplets generated when the first type is performed can be suppressed, the first type quasi-micro droplets having a mean particle size of about 20 to 30% or less and the second type quasi-micro droplets having a particle size of less than 10% are used. The particle size dispersion degree can be greatly improved to less than 5%.

Comparative example

  FIG. 49 shows a microchannel in a comparative example of the present invention. The micro-channel is formed on a Pyrex (registered trademark) glass substrate (1) having a size of 70 mm × 40 mm × 1 t (thickness), a continuous phase introduction channel (3) corresponding to the micro-channel, and a dispersed phase introduction channel ( 5) The width of the discharge flow path (7) is 200 μm and the depth is 100 μm, and the cross-phase (6) where the continuous phase introduction flow path and the dispersed phase introduction flow path intersect at an angle of 44 °. A letter-shaped channel was formed. The length of the discharge channel is 30 mm.

  The micro flow path is formed by general photolithography and wet etching, and the flow path of the glass substrate on which the flow path is formed corresponds to the flow path inlet (11) and the discharge port (8). A glass cover body having a thickness of 1 mm and a thickness of 70 mm × 20 mm provided with a small hole having a diameter of 0.6 mm in advance at a position using mechanical processing means was manufactured by thermal bonding in the same manner as in Example 1. Next, the microchannel structure is held by a holder, and a mixed solution of monomer (styrene), divinylbenzene, butyl acetate and benzoyl peroxide is used as a dispersed phase for generating microdroplets in the same manner as in Example 1. Was injected into a microsyringe as a continuous phase, and the solution was fed with a microsyringe pump to produce fine droplets. The liquid feeding speed is 1 μl / min for the dispersed phase and 15 μl / min for the continuous phase. Formation of microdroplets was observed at the intersection where the dispersed phase and continuous phase of the microchannel structure intersect, with both flow rates stabilized. When the generated microdroplets are observed, as shown in FIG. 50, the rear part of the microdroplets starts to collapse from a position after about 4 mm from the intersection of the continuous phase introduction flow path and the dispersed phase introduction flow path. It was observed that the droplets decomposed. As a result, the average particle size is 89.5 μm, the CV value (%) indicating the degree of dispersion of the particle size is 22.5%, and the micro droplets having a relatively non-uniform particle size with a particle size dispersion of 20% or more. Met.

  FIG. 44 shows a microchannel according to the fifth embodiment of the present invention. The micro-channel is formed on a Pyrex (registered trademark) glass substrate (1) having a size of 70 mm × 40 mm × 1 t (thickness), a continuous phase introduction channel (3) corresponding to the micro-channel, and a dispersed phase introduction channel ( 5) The width of the discharge channel (7) is 200 μm and the depth is 300 μm, and Y has an intersection (6) where the continuous phase introduction channel and the dispersed phase introduction channel intersect at an angle of 44 °. Two micro-channels are formed: a Y-shaped channel, and a Y-shaped channel having an intersection (6) where the continuous phase introducing channel and the dispersed phase introducing channel intersect at an angle of 22 °. did. Therefore, the present embodiment is an example in which the angle at the intersection of the continuous phase introduction flow path and the dispersed phase introduction flow path is changed in the second embodiment.

  The micro-channel is formed by general photolithography and dry etching, and corresponds to the inlet (11) and the outlet (8) of the channel on the surface of the glass substrate on which the channel is formed. A glass cover body having a thickness of 1 mm and a thickness of 70 mm × 20 mm provided with a small hole having a diameter of 0.6 mm in advance at a position using mechanical processing means was manufactured by thermal bonding in the same manner as in Example 1.

  Next, the microchannel structure is held by a holder, and a mixed solution of monomer (styrene), divinylbenzene, butyl acetate and benzoyl peroxide is used as a dispersed phase for generating microdroplets in the same manner as in Example 1. Was injected into a microsyringe as a continuous phase, and the solution was fed with a microsyringe pump to produce fine droplets. The liquid feeding speed is 1 μl / min for the dispersed phase and 15 μl / min for the continuous phase. Formation of microdroplets was observed at the intersection where the dispersed phase and continuous phase of the microchannel structure intersect, with both flow rates stabilized. When the generated micro droplets are observed, when the intersecting portions intersect at an angle of 22 °, the average particle diameter is 110.5 μm, and the CV value (%) indicating the degree of dispersion of the particle diameter is 8.7%. When the parts intersect at an angle of 44 °, the average particle size is 87.8 μm, the CV value (%) indicating the degree of dispersion of the particle size is 8.9%, and both have a particle size dispersion of less than 10%. Uniform fine droplets.

  As shown in Example 5, the particle size is controlled by changing the angle of the intersection of the dispersed phase introduction channel and the continuous phase introduction channel without changing the conditions of the liquid feeding speed of the dispersed phase and the continuous phase. It can be seen that it is possible.

It is the schematic which shows the microchannel which produces the conventional microparticles. It is A-A 'sectional drawing in the microchannel which produces | generates the conventional microparticle of FIG. It is a conceptual diagram showing a state when a micro droplet is generated and after it is generated, and when the average particle size of the micro droplet is larger than the width or depth of the channel, the micro droplet is generated. FIG. 6 is a conceptual diagram showing a state in which tailing occurs when the liquid droplets are crushed and the rear part of the micro droplet gradually collapses due to the shear stress of the continuous phase and the inner wall of the flow path. It is a conceptual diagram which shows the state when a microdroplet is produced | generated and after it is produced | generated, and a microdroplet is produced | generated when the average particle diameter of a microdroplet is small with respect to the width | variety or depth of a flow path. FIG. 6 is a conceptual diagram showing a state in which tailing occurs when the liquid droplets fall and the rear part of the micro droplet gradually collapses due to the shear stress of the continuous phase. It is a conceptual diagram which shows the state when a microdroplet is generated and after it is generated, and the average particle diameter of the microdroplet is smaller than the width or depth of the channel and the inner diameter of the channel at the time of droplet generation When the flow path width and depth are increased before the rear part of the microdroplet gradually collapses due to the shear stress of the continuous phase, no tailing occurs when the microdroplet is generated. It is the conceptual diagram which showed a mode that a droplet did not collapse. It is a conceptual diagram which shows the method of forming a microparticle by shearing a disperse phase by the shear force by the continuous phase and the inner wall of a flow path in the crossing part vicinity of a flow path. The continuous phase on both sides sandwiches the central dispersed phase in the vicinity of the intersection of the channels, and the dispersed phase is sheared by the shear force between the continuous phases on both sides and the upper and lower inner walls of the channel to form microparticles. It is a conceptual diagram which shows a method. It is a conceptual diagram showing a method in which a central continuous phase in the vicinity of an intersection of flow paths shears the dispersion on both sides with the shear force of the continuous phase and the inner wall of the flow path to form fine particles. In the vicinity of the intersection of the channels, a dispersed phase is introduced linearly from one side and a continuous phase is introduced from the other side, and the dispersed phase is sheared by the shearing force of the continuous phase and the inner wall of the channel to generate fine particles. It is a conceptual diagram showing a method of discharging in an arbitrary direction. When the dispersed phase is a two-phase two-layer laminar flow, it is a conceptual diagram showing a method of forming fine particles by shearing the dispersed phase between the continuous phase and the inner wall of the channel near the intersection of the channels. . FIG. 5 is a conceptual diagram showing a method of forming microparticles by shearing a dispersed phase between the continuous phase and the inner wall of the flow path in the vicinity of the intersection of flow paths as a reaction liquid obtained by reacting 2 liquids in the dispersed phase. A conceptual diagram showing a method for forming a microparticle by shearing a dispersed phase between the continuous phase and the inner wall of the flow path in the vicinity of the intersection of the flow paths as a reaction liquid obtained by reacting two liquids of the dispersed phase and the continuous phase. is there. It is a conceptual diagram which shows the method of forming a microparticle by shearing a dispersed phase by the said continuous phase and the inner wall of a flow path in the vicinity of the cross | intersection part of a flow path as 4 phase laminar flow which a dispersed phase consists of 4 liquids. It is the schematic which showed the method of providing a light irradiation means outside and hardening a microparticle by light irradiation. It is the schematic which showed the method of hardening a microparticle by the light irradiation to a flow path using a mask. It is the schematic which showed the method of providing a heating means outside and hardening a microparticle by heating. It is the schematic which showed the method of providing a heating means in a microchannel structure, and hardening a microparticle by heating. It is the conceptual diagram which showed the mode of the production | generation of a microparticle in the case of a flow path in which the flow path width and flow path depth are sufficiently larger than the average particle diameter of the produced | generated microdroplet. It is B-B 'sectional drawing of the flow path in FIG. It is the conceptual diagram which showed the mode of the production | generation of a microparticle when a continuous phase introduction flow path and a discharge flow path are not microchannels. It is C-C 'sectional drawing of the flow path in FIG. It is D-D 'sectional drawing of the flow path in FIG. Generation of microparticles when the depth and / or width of the discharge channel from the intersection where the dispersed phase and continuous phase intersect to the discharge port is larger than the depth and / or width of the channel through which the dispersed phase flows It is the conceptual diagram which showed. It is E-E 'sectional drawing of the flow path in FIG. It is F-F 'sectional drawing of the flow path in FIG. It is the conceptual diagram which showed the production | generation of the microparticle when the depth and / or width of a discharge channel become large from the middle, and the position where the depth and / or width of a discharge channel becomes large is the produced | generated microdroplet. FIG. 27 is a conceptual diagram showing generation of microparticles in a case where the microparticles are located at a position separated by a crossing portion where a dispersed phase and a continuous phase intersect rather than a position where the rear part of the microdroplet begins to collapse. The auxiliary line (broken line) corresponds to the auxiliary line (broken line) in FIG. It is the conceptual diagram which showed the production | generation of the microparticle when the depth and / or width | variety of a discharge channel become large from the middle, and the production | generation of a microparticle when it exists in the position closer to the cross | intersection part where a disperse phase and a continuous phase cross The two auxiliary lines (broken lines) in FIG. 27 correspond to the auxiliary lines (broken lines) in FIG. It is the conceptual diagram which showed the example of the microchannel structure which formed the 1 or more protrusion from any one of the bottom face of a flow path, an upper surface, and a side surface, or 2 or more surfaces. FIG. 29 is an enlarged view of the vicinity of the intersection 6 in FIG. 28, and is a conceptual diagram illustrating an example of a microchannel structure in which one or more protrusions are formed from the bottom surface of the channel. FIG. 30 is a G-G ′ sectional view of the flow path in FIG. 29. FIG. 29 is an enlarged view of the vicinity of the intersection 6 in FIG. 28, and is a conceptual diagram illustrating an example of a micro-channel structure in which one or more protrusions are formed from the upper surface of the channel. FIG. 32 is a cross-sectional view taken along the line H-H ′ of FIG. 31. FIG. 29 is an enlarged view of the vicinity of the intersection 6 in FIG. 28, and is a conceptual diagram illustrating an example of a micro-channel structure in which one or more protrusions are formed from the bottom and side surfaces of the channel. It is J-J 'sectional drawing of the flow path in FIG. FIG. 29 is an enlarged view of the vicinity of the intersection 6 in FIG. 28, and is a conceptual diagram illustrating an example of a micro-channel structure in which one or more protrusions are formed from the bottom, top, and side surfaces of the channel. FIG. 36 is a K-K ′ sectional view of the flow path in FIG. 35. It is a conceptual diagram which shows the microchannel in a 1st Example. It is L-L 'sectional drawing of the flow path in FIG. It is M-M 'sectional drawing of the flow path in FIG. It is a conceptual diagram which shows the microchannel structure in a 1st Example. It is a figure explaining the micro droplet manufacturing method in a 1st Example. It is a figure which shows the mode of the production | generation of the micro droplet observed in the 1st Example. It is the micro droplet produced | generated in the 1st Example. FIG. 10 is a conceptual diagram showing a micro flow channel in Example 5. FIG. 5 is a conceptual diagram showing a micro flow channel in Example 2. FIG. 6 is a conceptual diagram showing a microchannel in Example 4. It is an enlarged view of the cross | intersection part 6 vicinity in the flow path of FIG. FIG. 6 is a conceptual diagram showing a micro flow channel in Example 3. It is a conceptual diagram which shows the microchannel in a comparative example. FIG. 50 is an enlarged view of the vicinity of the intersection 6 in the flow path of FIG. 49, and shows a state of generation of microdroplets. It is an example of the micro channel structure which constituted the substrate which has a channel in three dimensions. It is O-O 'sectional drawing in the microchannel structure of FIG. It is P-P 'sectional drawing in the microchannel structure of FIG.

Explanation of symbols

1: Substrate 2: Continuous phase introduction port 3: Continuous phase introduction channel 4: Dispersed phase introduction port 5: Dispersed phase introduction channel 6: Intersection 7: Discharge channel 8: Discharge port 9: Microchannel width 10 : Continuous phase 11: Inlet 12: Type 1 quasi-microdroplet 13: Type 2 quasi-microdroplet 14: Position where the rear part of the microdroplet begins to collapse 15: Dispersed phase 16: Microchannel 17: Microparticle 18: Diameter of fine particles 19: Micro-channel structure 20: Light irradiation spot 21: Light irradiation 22: Mask 23: Holder 24: Position where the depth and / or width of the channel increases 25: Inner wall 26 of the channel : Beaker 27: Teflon (registered trademark) tube 28: Heater 29: Common channel 30: Cover body 31: Trailing 32: Upper cover body 33: Lower cover body 34: Micro droplet 35: Channel 36: Fillet joint 37 : Micro syringe pump 38: Micro syringe 39: flow channel width 40: channel depth

Claims (6)

  1. An introduction port and an introduction channel for introducing a dispersed phase, an introduction port and an introduction channel for introducing a continuous phase, a discharge channel for discharging fine particles generated by the dispersed phase and the continuous phase, and A micro-channel structure comprising a channel having a discharge port, and supplying a continuous phase in a direction that intersects the dispersed phase flowing through the microchannel at an arbitrary angle with respect to the flow of the dispersed phase. The fine particles are generated from the dispersed phase by the shearing force of the continuous phase and the wall surface in the flow path, the diameter of the fine particles is controlled , and the discharge port from the intersection where the dispersed phase and the continuous phase intersect A position where the depth and / or width of the discharge flow channel leading to is larger than the depth and / or width of the flow channel through which the dispersed phase flows and larger than the depth and / or width of the flow channel through which the dispersed phase flows. The generated microdroplet is smaller than the microdroplet. Fine channel device, characterized in that there are in the position before disassembling the microdroplets.
  2. In a part of the discharge flow path from the intersection where the dispersed phase and the continuous phase intersect to the discharge port, the width of the discharge flow path is narrow and the width of the discharge flow path is narrow 2. The microchannel structure according to claim 1 , wherein the microchannel structure is at or near the intersection of a dispersed phase and a continuous phase flowing in the microchannel.
  3. 3. The microchannel structure according to claim 2 , wherein the portion where the width of the discharge channel is narrow is on the introduction channel side of the dispersed phase at the intersection of the dispersed phase flowing in the microchannel and the continuous phase. .
  4. In the vicinity of an intersection of the dispersed and continuous phases flowing in microchannels, the bottom surface of the flow path, from the top and / or side, more of claims 1 to 3, characterized in that one or more projections are formed A microchannel structure according to any one of the above.
  5. The microparticle manufacturing method which produces | generates a microparticle using the microchannel structure in any one of Claims 1-4 .
  6. According to claim 5, characterized in that controlling the particle size of the fine particles produced by changing the angle of the introduction channel crosses for introducing a continuous phase and a dispersed phase introduction channel for introducing A method for producing fine particles.
JP2003386796A 2003-11-17 2003-11-17 Microchannel structure and microparticle manufacturing method using the same Active JP4042683B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2003386796A JP4042683B2 (en) 2003-11-17 2003-11-17 Microchannel structure and microparticle manufacturing method using the same

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP2003386796A JP4042683B2 (en) 2003-11-17 2003-11-17 Microchannel structure and microparticle manufacturing method using the same

Publications (2)

Publication Number Publication Date
JP2005144356A JP2005144356A (en) 2005-06-09
JP4042683B2 true JP4042683B2 (en) 2008-02-06

Family

ID=34694381

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2003386796A Active JP4042683B2 (en) 2003-11-17 2003-11-17 Microchannel structure and microparticle manufacturing method using the same

Country Status (1)

Country Link
JP (1) JP4042683B2 (en)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9039273B2 (en) 2005-03-04 2015-05-26 President And Fellows Of Harvard College Method and apparatus for forming multiple emulsions
JP2007009074A (en) * 2005-06-30 2007-01-18 Sanyo Chem Ind Ltd Method for producing resin particle
JP2007031604A (en) * 2005-07-28 2007-02-08 Sanyo Chem Ind Ltd Production method for resin particle
JP2007031603A (en) * 2005-07-28 2007-02-08 Sanyo Chem Ind Ltd Method for producing resin particle
JP4627302B2 (en) * 2007-01-09 2011-02-09 株式会社神戸製鋼所 Method and apparatus for producing fine particles
JP4803495B2 (en) * 2007-01-09 2011-10-26 独立行政法人農業・食品産業技術総合研究機構 Method and apparatus for manufacturing shelled microbubbles
JP4972726B2 (en) * 2007-03-28 2012-07-11 国立大学法人 岡山大学 Phase inversion temperature emulsification apparatus and emulsification method
EP2142314A4 (en) * 2007-03-30 2012-04-25 Fujifilm Corp Method of cleaning micro-flow passages
JP2009014377A (en) * 2007-07-02 2009-01-22 Tosoh Corp Cellulose particles and their manufacturing method
JP5023902B2 (en) * 2007-09-06 2012-09-12 株式会社日立プラントテクノロジー Emulsifying device
JP4572973B2 (en) * 2008-06-16 2010-11-04 ソニー株式会社 Microchip and flow-feeding method in microchip
JP5196304B2 (en) 2008-07-29 2013-05-15 大日本印刷株式会社 Emulsion-forming microchip and method for producing the same
US9713802B2 (en) 2009-01-13 2017-07-25 Kobe Steel, Ltd. Method and apparatus for manufacturing liquid microspheres
US20120199226A1 (en) * 2009-09-02 2012-08-09 Basf Se Multiple emulsions created using junctions
JP5691195B2 (en) 2010-03-01 2015-04-01 ソニー株式会社 Microchip and fine particle analyzer
EP2714254B1 (en) 2011-05-23 2017-09-06 President and Fellows of Harvard College Control of emulsions, including multiple emulsions
WO2013006661A2 (en) 2011-07-06 2013-01-10 President And Fellows Of Harvard College Multiple emulsions and techniques for the formation of multiple emulsions
JP6140524B2 (en) * 2013-05-20 2017-05-31 株式会社フジクラ Droplet generator
JP5897681B2 (en) * 2014-10-08 2016-03-30 ソニー株式会社 Microchip and fine particle analyzer
KR101961526B1 (en) * 2016-12-13 2019-03-25 경희대학교 산학협력단 Anisotropic particle and manufacturing method thereof

Also Published As

Publication number Publication date
JP2005144356A (en) 2005-06-09

Similar Documents

Publication Publication Date Title
Paik et al. Electrowetting-based droplet mixers for microfluidic systems
Barrero et al. Micro-and nanoparticles via capillary flows
Lee et al. Passive mixers in microfluidic systems: A review
US6890093B2 (en) Multi-stream microfludic mixers
US6877892B2 (en) Multi-stream microfluidic aperture mixers
Khan et al. Microfluidic synthesis of colloidal silica
Mazutis et al. A fast and efficient microfluidic system for highly selective one-to-one droplet fusion
Nisisako et al. Synthesis of monodisperse bicolored janus particles with electrical anisotropy using a microfluidic Co‐Flow system
US6377387B1 (en) Methods for producing droplets for use in capsule-based electrophoretic displays
US20090090422A1 (en) Method for Treating Drops in a Microfluid Circuit
US9038919B2 (en) Formation and control of fluidic species
JPWO2005089921A1 (en) Method and apparatus for generating microdroplets
US9486757B2 (en) Scale-up of microfluidic devices
Ward et al. Mixing in microfluidic devices and enhancement methods
US6305834B1 (en) Method and device for producing a dispersed mixture via crossing partial flows
JP5362552B2 (en) Process for processing and / or forming non-Newtonian fluids using microchannel process technology
Vladisavljević et al. Industrial lab-on-a-chip: Design, applications and scale-up for drug discovery and delivery
US20030198130A1 (en) Fluidic mixer in microfluidic system
Link et al. Electric control of droplets in microfluidic devices
TWI451903B (en) Multiple flow path microrector design
EP1481724A1 (en) Reaction method using microreactor
JPWO2002068104A1 (en) Method and apparatus for producing emulsion and microcapsule
Doku et al. On-microchip multiphase chemistry—a review of microreactor design principles and reagent contacting modes
CA2650499C (en) Flow distribution channels to control flow in process channels
Abate et al. Faster multiple emulsification with drop splitting

Legal Events

Date Code Title Description
A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20070725

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20070731

A521 Written amendment

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20070926

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20071023

R151 Written notification of patent or utility model registration

Ref document number: 4042683

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R151

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20071105

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20101122

Year of fee payment: 3

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20111122

Year of fee payment: 4

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20111122

Year of fee payment: 4

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20121122

Year of fee payment: 5

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20131122

Year of fee payment: 6