JP2004202476A - Particle manufacturing method and microchannel structure therefor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a particle production method which can be desirably used for the production of e.g., small liquid drops or gel particles used in e.g., a packing for a collection or separation column, which method permits the formation of particles in a microchannel and the formation of particles in various combination of a disperse phase and a continuous phase, and can cope with industrial mass production and to provide a microchannel structure therefor. <P>SOLUTION: The particle production method comprises continuously introducing a disperse phase and at least two continuous phases into a structure having a microchannel and meanwhile bringing the disperse phase and the continuous phases into contact with each other under shear to form small particles. The microchannel structure therefor is also provided. <P>COPYRIGHT: (C)2004,JPO&NCIPI

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention is a particle production method suitably used for producing fine droplets and gel particles used for column packing for separation and separation, and also produces particles such as fine droplets. For a microchannel structure for use.
[0002]
[Prior art]
In recent years, using a microchannel structure having a microchannel with a length of about several cm, a width and a depth of sub μm to several hundred μm on a glass substrate or a resin substrate of several cm square, Attention has been paid to research for producing fine particles by liquid transfer. (See, for example, Non-Patent Documents 1 and 2)
Regarding the particle generation technology in the microchannel, as shown in FIG. 1, a continuous phase introduction port 2, a continuous phase introduction channel 3, a dispersed phase introduction port 4, and a dispersed phase introduction flow are provided on a microchannel substrate 1. It is a T-shaped structure having a passage 5, a discharge channel 7, and a discharge port 8, and a junction 6 exists at a portion where the introduced continuous phase and the dispersed phase merge. The depth of each channel is 100 μm, the width of the introduction channel for introducing the dispersed phase is 100 μm, and the width of the introduction channel for introducing the continuous phase is 300 to 500 μm. When the flow rate of the continuous phase is controlled (controlled) and the liquid is sent, extremely uniform fine particles can be generated at a point where the dispersed phase and the continuous phase merge through the flow path (merging portion). Further, by controlling the flow rates of the dispersed phase and the continuous phase, it is possible to control the produced particle diameter. However, in this method, there was a problem that as the liquid sending speed of the dispersed phase was increased, stable particle generation could not be obtained, and finally a laminar flow could not be generated. In addition, since the channel forming material is made of glass such as blue plate, quartz, Pyrex (registered trademark) or Si, when the dispersed phase is a liquid showing hydrophobicity and the continuous phase is a liquid showing hydrophilicity, the laminar flow It was substantially difficult to generate particles because the formation was more stable than particle generation.
[0003]
In order to solve this problem and generate fine particles, attempts have been made to solve the problem by surface treatment, but over a long period of time, particles could not be generated, and further improvement was required. .
[Non-patent document 1]
Takashi Nishisako et al., "Creation of microdroplets in liquid in microchannel", 4th Conference on Chemistry and Microsystems, 2001, p. 59 [Non-Patent Document 2]
TAKASI NISISAKO et al., "DROPLET FORMATION IN A MICRO CHANNEL ON PMMA PLATE", Micro Total Analysis System, 2001, pp. 137-138.
[Problems to be solved by the invention]
As described above, the conventional technology for generating particles such as droplets in a microchannel can generate extremely uniform particles at the junction of a continuous phase and a dispersed phase in a T-shaped microchannel. As the flow velocity increased, the particle phenomena became unstable and eventually became laminar. In addition, there is a problem of affinity between the dispersed phase liquid and the wall surface of the microchannel, which is a problem when producing particles of various liquids, and further improvement has been demanded in the case of industrial mass production.
[0005]
The present invention has been made in view of the above-described problems, and enables generation of particles in a microchannel, and generation of particles in a combination of various dispersed phases and continuous phases. An object of the present invention is to provide a method for producing particles that can be used for mass production and a microchannel structure for the method.
[0006]
[Means for Solving the Problems]
The present invention solves the above-mentioned problem by continuously introducing a dispersed phase and two or more continuous phases into a structure having a microchannel, and converging a portion where the dispersed phase and the continuous phase join (hereinafter, referred to as a “joining”). Part)), and found that the dispersed phase was formed into fine droplets, that is, formed into fine particles by bringing the dispersed phase into contact with the continuous phase and shearing the dispersed phase. In order to generate a dispersion phase, an introduction port for introducing a dispersed phase and an introduction flow path communicating therewith, two or more introduction ports for introducing a continuous phase and an introduction flow path communicated therewith, and two or more dispersion phases A discharge channel comprising a microchannel for discharging particles generated by the continuous phase and a discharge port communicating therewith are provided, and the aspect ratio (ratio of depth / width of the flow channel) of the cross section of the discharge channel is provided. It was also found that the value was set to 0.30 or more. It is possible to solve the problems caused by technology, has led to the completion of the finally the present invention.
[0007]
That is, the present invention provides a method for forming fine particles by contacting the dispersed phase and the continuous phase and shearing the dispersed phase while continuously introducing the dispersed phase and two or more continuous phases into the structure having the microchannel. And a structure for achieving this, an introduction port for introducing a dispersed phase and an introduction flow path communicating therewith, and an introduction port for introducing a continuous phase and the same. A microchannel structure comprising: an introduction channel that communicates with a discharge channel composed of a microchannel for discharging particles generated by a dispersed phase and two or more continuous phases; and a discharge port that communicates with the microchannel. The aspect ratio (depth / width ratio of the flow path) of the cross section of the discharge flow path is 0.30 or more.
[0008]
In the present specification, “particles” may mean not only liquid droplets, that is, liquid droplets, but also solid particles that have been cured.
[0009]
Hereinafter, the present invention will be described in detail.
<Particle production method>
As described above, the method for producing particles according to the present invention includes the steps of: continuously introducing a disperse phase and two or more continuous phases into a structure having microchannels; This is a method of forming fine particles by shearing.
[0010]
The dispersed phase used in the present invention is a liquid material for producing particles by a microchannel structure, for example, a monomer for polymerization such as styrene, a crosslinking agent such as divinylbenzene, and a gel such as a polymerization initiator. Refers to a medium in which raw materials for production are dissolved in a suitable solvent. Here, as the disperse phase, the purpose of the present invention is to efficiently generate fine particles, and if the purpose is to achieve this purpose, any liquid phase can be sent through the flow path in the fine flow path structure. There is no particular limitation on the components, as long as the particles can be further formed. Also, a slurry in which a solid material is partially mixed in the dispersed phase may be used.
[0011]
The continuous phase used in the present invention is a liquid substance used for generating particles from the dispersed phase by the microchannel structure, and for example, a dispersant for gel production such as polyvinyl alcohol is dissolved in an appropriate solvent. Refers to the medium. Here, as the continuous phase, similarly to the dispersed phase, there is no particular limitation as long as it can feed the flow path in the microchannel structure, and the component is not particularly limited as long as particles can be formed, If two or more of the continuous phases have the same composition, the composition of the medium around the particles generated by the dispersed phase can be uniform or controlled, and the generated particles can be taken out, irradiated with light, or heated. Is easy to carry out, which is preferable. Further, a slurry in which a solid material is partially mixed in the continuous phase may be used.
[0012]
Further, in order to form particles, the dispersed phase and the continuous phase need to be substantially non-compounding or not compatible.For example, when an aqueous phase is used as the dispersed phase, An organic phase such as butyl acetate that is substantially insoluble in water will be used. When an aqueous phase is used as the continuous phase, the reverse is true.
[0013]
In the present invention, while continuously introducing the dispersed phase and the continuous phase into the microchannel structure described below, the dispersed phase and the continuous phase are brought into contact with each other at the junction where the two are merged, and the dispersed phase is sheared. The particle diameter of the generated particles is controlled by changing the angle at which the introduction channel for introducing the dispersed phase and the introduction channel for introducing the continuous phase intersect. It is possible to do. This is easier to control in the production of particles using a conventional structure than changing the introduction speed of the dispersed phase and the continuous phase and is suitable for industrial mass production. Furthermore, by making the introduction speeds of the dispersed phase and the continuous phase introduced into the microchannel structure substantially the same, industrial mass production is achieved in terms of controlling the particle size of the generated particles and simplifying the production equipment. It can fully respond to.
<Microchannel structure>
The microchannel structure of the present invention is a structure for performing the above-described particle production, and an introduction port for introducing a dispersed phase and an introduction channel communicating therewith, for introducing a continuous phase. An inlet and an inlet channel communicating therewith, a discharge channel comprising a microchannel for discharging particles generated by the dispersed phase and the two or more continuous phases, and an outlet communicating therewith; It has a structure in which the aspect ratio of the road cross section (the ratio of the depth / width of the flow path) is 0.30 or more.
[0014]
Here, the inlet for introducing the disperse phase means an opening for introducing the disperse phase, and a mechanism for continuously introducing the disperse phase may be provided by providing an appropriate attachment to the inlet. Similarly, the introduction port for introducing the continuous phase also means an opening for introducing the continuous phase, and a mechanism for continuously introducing the continuous phase by providing an appropriate attachment to this introduction port. Good.
[0015]
The introduction flow path for introducing the dispersed phase communicates with the introduction port, and the dispersed phase is introduced and sent along the introduction flow path. Although the shape of the introduction channel has an effect on controlling the shape and particle size of the particles, the width is formed to be several hundred μm or less, and similarly, the introduction channel for introducing the continuous phase also has the same shape as the introduction port. A continuous phase is introduced and communicated along this introduction flow path. The shape of the introduction channel has an effect on controlling the shape and the particle diameter of the particles, but the width may be several hundreds μm or less. In addition, the flow path of each continuous phase and the dispersed phase may have a shape in which the continuous phase can be introduced across the dispersed phase and crosses toward one point of the flow path of the dispersed phase.
[0016]
The discharge flow path communicates with the above three introduction flow paths and the discharge port. After the dispersed phase and the continuous phase merge, the liquid is sent along the discharge flow path and discharged from the discharge port. Although the shape of the discharge channel is not particularly limited, the width may be several hundreds μm or less, and may be a Y-shape including the inlet channel. The outlet means an opening for discharging the generated particles, and furthermore, a suitable attachment may be provided at the outlet to provide a mechanism for continuously discharging the phase containing the generated particles.
[0017]
Note that these channels may be referred to as minute channels in this specification.
[0018]
Furthermore, in the microchannel structure of the present invention, the introduction channel for introducing the dispersed phase and the two or more introduction channels for introducing the continuous phase intersect at an arbitrary angle, and these three or more It is preferable that the introduction flow path has a structure that connects to the discharge flow path at an arbitrary angle. By setting the angle at which the three or more introduction flow paths intersect to an arbitrary angle, the particles generated at the junction are controlled to have a desired particle diameter, and the particle generation point is set so that the particles are generated near the junction. Can be controlled. The setting of the intersection angle may be appropriately determined according to the particle diameter of the target particles and the flow rate at the time of generation.
[0019]
Regarding the cross-sectional shape of the introduction flow path and the discharge flow path, the aspect ratio of the flow path cross section is preferably 0.30 or more, and more preferably 0.30 or more and less than 3.0. If the aspect ratio is within this range, uniform particles can be generated at the junction. Deviating from this range, if the aspect ratio is less than 0.30, it may be difficult to generate uniform particles. However, this is not a limitation as long as the produced particle diameter is equal to or less than the flow channel depth.
[0020]
Furthermore, when the width and depth of the introduction flow path for introducing the dispersed phase and the introduction flow path for introducing the continuous phase are equal, in addition to the above effects, the design of the micro flow path structure becomes easy, In addition, the control during liquid feeding becomes easier, which is suitable for industrial mass production.
[0021]
In the relationship between the width of the introduction flow path and the width of the discharge flow path, if the width of the introduction flow path is equal to or greater than the width of the discharge flow path, the width of the introduction flow path is smaller than the width of the discharge flow path. Even if the number of particles is increased, uniform particles can be generated at the merging portion, and the effect of increasing the particle generation speed can be obtained, which is a preferable embodiment.
[0022]
As the width of the discharge channel, it is preferable that the width of the discharge channel is narrow at a part of the discharge channel from the intersection of the dispersed phase and the continuous phase to the discharge port. That is, during the process up to the particle discharge port, the flow is formed by partially narrowing at the junction of the introduction flow path and the discharge flow path, or by forming the flow path configuration wall along the dispersed phase flow path convex. Even if the liquid flow rate is increased, uniform particles can be generated at the junction and a rise in the liquid sending pressure can be reduced, which is a preferable embodiment.
[0023]
The microchannel structure of the present invention has the above-described structure and performance, but has three or more introduction parts and introduction channels for introducing the dispersed phase and the continuous phase, and three or more introduction flows. A junction where the paths intersect, a microchannel structure having a discharge channel and a discharge port for discharging the liquid, a substrate having a microchannel formed on at least one surface, and a microchannel formed. A cover body in which at least four or more small holes for communicating the microchannel and the outside of the microchannel structure are arranged at a predetermined position of the microchannel so as to cover the substrate surface which has been formed, is laminated and integrated. May be. As a result, fluid can be introduced from the outside of the microchannel structure to the microchannel, and can be discharged again to the outside of the microchannel structure. It is possible to pass through the minute channel. Fluid delivery is enabled by mechanical means such as a micropump.
[0024]
As a material of the substrate and the cover body in which the minute flow path is formed, a material which can form the minute flow path, has excellent chemical resistance, and has appropriate rigidity is preferable. For example, it may be glass, quartz, ceramic, silicon, metal or resin. The size and shape of the substrate and the cover are not particularly limited, but the thickness is desirably about several mm or less. When the small hole arranged in the cover body communicates the microchannel with the outside of the microchannel structure and is used as a fluid inlet or outlet, it is desirable that its diameter is, for example, several mm or less. The small holes in the cover body can be processed chemically, mechanically, or by various means such as laser irradiation or ion etching.
[0025]
Further, in the microchannel structure of the present invention, the substrate on which the microchannel is formed and the cover are laminated and integrated by means such as heat bonding or bonding using an adhesive such as a photo-curing resin or a thermosetting resin. be able to.
[0026]
BEST MODE FOR CARRYING OUT THE INVENTION
Hereinafter, examples of the present invention will be described, and embodiments of the present invention will be described in more detail. It is needless to say that the present invention is not limited to the following embodiments, and can be arbitrarily changed without departing from the gist of the present invention.
Further, in the embodiment, one fine channel is formed on one substrate. However, in the case of industrial mass production, a large number of micro channels are formed on one substrate, or many micro channels are formed. This becomes possible by laminating one substrate.
(Example 1)
FIG. 2 shows a microchannel for producing particles according to the first embodiment of the present invention. The fine channels are formed on a 70 mm × 20 mm × 1 t (thickness) Pyrex (registered trademark) glass, and the widths of the continuous phase introduction channel 3, the dispersed phase introduction channel 5, and the discharge channel 7, which correspond to the micro channels, are set. Each of them has a fine channel shape of 140 μm, a depth of 60 μm, and an aspect ratio of a micro channel = 0.43, and a junction where the continuous phase introduction channel 3 and the dispersed phase introduction channel 5 intersect at an angle of 22 degrees. One flow path having a shape having the shape was formed. The width and depth of the microchannel depend on the particle diameter of the droplet to be generated, but it is sufficient that the aspect ratio of the microchannel does not deviate from 0.3 or more and less than 3.
[0027]
This Y-shaped particle production microchannel structure was produced as follows in accordance with the production procedure shown in FIG. On one surface of a glass substrate 9 having a thickness of 1 mm and a size of 70 mm × 20 mm, a metal film 10 such as gold is formed to a thickness such that exposure light to be described later is not transmitted (FIG. 3A). ), And a photoresist 11 was coated on the metal film (FIG. 3B). Further, a photomask 12 having a pattern depicting the shape of the microchannel was placed on the photoresist, and the photoresist was exposed and developed from above the photomask (FIG. 3 (c) exposure-development step). Next, after etching the metal film 10 with an acid or the like (FIG. 3D metal film etching step), the resist and glass are etched with hydrofluoric acid or the like (FIG. 3E resist and glass etching step), Further, the remaining metal film 10 was dissolved with an acid or the like (FIG. 3 (f) metal film removal step) to obtain a substrate 13 on which a fine channel was formed. In the embodiment, the minute flow path is formed by etching the glass substrate to form the minute flow path, but the production method is not limited to this.
[0028]
On the surface of the substrate 13 having the microchannels having the microchannels, a diameter of 0 μm is previously set at a position corresponding to the fluid inlets (continuous phase inlet 2 and dispersed phase inlet 4) and the fluid outlet 8 of the microchannel. A small hole having a diameter of 0.6 mm was thermally bonded to a glass cover body 14 having a thickness of 1 mm and a size of 70 mm × 20 mm provided by using a mechanical processing means, and as shown in FIG. The structure was manufactured. In the embodiment, the glass substrate is used for the substrate forming the microchannel and the cover body, but the present invention is not limited to this.
[0029]
Next, the method for producing particles of the present invention will be described. As shown in FIG. 5, the liquid is held by a holder 16 or the like so that the liquid can be sent to the droplet generation microchannel structure 15, and the Teflon (registered trademark) tube 18 and the fillet joint 19 are fixed to the holder 16. . The other end of the Teflon (registered trademark) tube 18 is connected to micro syringes 21, 22, 23. This allows liquid to be sent to the microchannel structure 15 for particle production. Next, a mixed solution of monomer (styrene), divinylbenzene, butyl acetate and benzoyl peroxide was injected into a micro syringe 23 as a dispersion phase for producing particles, and a 3% aqueous solution of polyvinyl alcohol was injected into micro syringes 21 and 22 into a continuous phase. The solution was injected, and the solution was sent by the micro syringe pump 20. The liquid sending flow rate is 6 μl / min for both the dispersed phase and the continuous phase. In a state where both the liquid sending flow rates are stable, the generation of particles is observed at the junction where the dispersed phase and the continuous phase of the microchannel structure for particle production 15 intersect. When the generated particles 23 were observed, they were extremely uniform particles having an average particle diameter of 77 μm as shown in FIG.
(Example 2)
FIG. 4 shows a microchannel for producing particles according to the second embodiment of the present invention. The microchannels are formed on a 70 mm × 20 mm × 1 t (thickness) polyetherimide substrate, and the widths of the continuous phase introduction channel 3, the dispersed phase introduction channel 5, and the discharge channel 7, which correspond to the microchannels, are all small. It has a fine channel shape of 140 μm, a depth of 60 μm, and a micro channel aspect ratio = 0.43, and has a junction where the continuous phase introduction channel 3 and the dispersed phase introduction channel 5 intersect at an angle of 22 degrees. One flow path having a curved shape was formed. Using the same photomask and technique as those described in Example 1, a flow path was formed on a 200 mm diameter Pyrex (registered trademark) glass substrate, a Ni thin film was formed, and a 300 μm thick film was formed by electroplating. A stamper was prepared and set in a mold of a molding machine, and a polyetherimide resin was prepared by an injection molding method. The prepared channel substrate was cut out at 70 mm × 20 mm × 1 t. The width and depth of the microchannel depend on the particle diameter to be generated, but it is sufficient that the aspect ratio of the microchannel does not deviate from the range of 0.3 or more and less than 3.
[0030]
As shown in FIG. 5, the liquid is held by a holder 16 or the like so that the liquid can be sent to the microchannel structure 15 for particle production, and a Teflon (registered trademark) tube 18 and a fillet joint 19 are fixed to the holder 16. The other end of the Teflon (registered trademark) tube 18 is connected to micro syringes 21, 22, 23. This allows liquid to be sent to the microchannel structure 15 for particle production. Next, a mixed solution of monomer (styrene), divinylbenzene, butyl acetate and benzoyl peroxide was injected into a micro syringe 23 as a dispersion phase for producing particles, and a 3% aqueous solution of polyvinyl alcohol was injected into micro syringes 21 and 22 into a continuous phase. The solution was injected, and the solution was sent by the micro syringe pump 20. The liquid sending flow rate is 6 μl / min for both the dispersed phase and the continuous phase. In a state where both the liquid sending flow rates are stable, the generation of particles is observed at the junction where the dispersed phase and the continuous phase of the microchannel structure for particle production 15 intersect. Observation of the generated particles 23 revealed that they were extremely uniform particles having an average particle diameter of 77 μm as shown in FIG.
(Example 3)
Next, a microchannel for particle production in Example 3 is shown in FIG. As in the case of Example 1, the microchannel is a glass of 70 mm × 20 mm × 1 t (thickness), and the continuous phase introduction channel 3, the dispersed phase introduction channel 5, and the discharge channel 7 are all 140 μm in width and depth. A Y-shape having a diameter of 60 μm and a microchannel having an aspect ratio = 0.43, and having a junction where the continuous phase introduction channel 3 and the dispersed phase introduction channel 5 intersect at an angle of 44 degrees. One channel is formed, and as shown in FIG. 11, when the intersection angle between the dispersed phase and the continuous phase is less than 90 degrees, that is, when the upstream of the channel of the dispersed phase and the continuous phase is on the same side, two Protrusions 24 are provided at the continuous phase flow path outlet or discharge flow path inlet at the intersection of both flow paths where each flow path of the continuous phase merges with the dispersed phase flow path, and the flow path width is locally narrowed. A structure in which the flow is temporarily stopped and the direction of the flow changes, causing the dispersed phase to be sheared and granulated near the junction. It was. The production procedure of the microchannel structure for producing particles was the same as that of Example 1. Next, in the same manner as in Example 1, the microchannel structure for particle production is held by a holder, and fixed and connected to a Teflon (registered trademark) tube, a fillet joint, and a micro syringe pump. A mixed solution of a monomer (styrene), divinylbenzene, butyl acetate, and benzoyl peroxide was injected into a dispersed phase for forming particles, and a 3% aqueous solution of polyvinyl alcohol was injected into a microsyringe into a continuous phase, and liquid was sent. The liquid sending flow rate is 6 μl / min for both the dispersed phase and the continuous phase.
[0031]
When the junction where the dispersed phase and the continuous phase of the microchannel structure for particle generation intersect with each other in a state where the flow velocity is stable is observed, as shown in FIG. 12, the particles 25 generated in the vicinity of the junction have a particle diameter of about 70 μm. Was produced stably, and the dispersibility was improved to 5% as compared with the case of Example 1. In Example 3, a protruding structure was provided as a method of narrowing the outlet of the continuous phase or the inlet of the discharge channel. However, the dispersed phase was sheared while damping the continuous phase, and the particle generation location was near the junction. The structure is not limited to this method as long as it has a similar effect, and a method of providing a protrusion in the flow path or constricting the flow path may be used.
[0032]
Further, as shown in FIG. 13, the angle at which the introduction flow path for introducing the dispersed phase and the introduction flow path for introducing the continuous phase intersect with each other is 90 degrees or more, that is, the upstream sides of the flow paths of the dispersed phase and the continuous phase are opposite. On the side, the continuous phase becomes a flow that pushes up the dispersed phase, so that the combination of the intersection angle and the flow velocity can be adjusted to bring the particle generation location in the flow path closer to the junction of both flow paths.
(Comparative Example 1)
Next, a microchannel for producing particles in Comparative Example 1 is shown in FIG. As in Example 1, the microchannels were formed on a 70 mm × 20 mm × 1 t (thickness) Pyrex (registered trademark) glass and the widths of the continuous phase introduction channel 3, the dispersed phase introduction channel 5, and the discharge channel 7 were changed. Each of them has a Y-shape of 140 μm, a depth of 60 μm, and an aspect ratio of the microchannel = 0.43, and a junction where the continuous phase introduction channel 3 and the dispersed phase introduction channel 5 intersect at an angle of 44 degrees. One flow path having the same shape was formed. The production procedure of the microchannel structure for producing particles was the same as that of Example 1.
[0033]
Next, as shown in FIG. 10, the microchannel structure for particle production is held by a holder, and fixed and connected to a Teflon (registered trademark) tube, a fillet joint, and a micro syringe pump. A mixed solution of a monomer (styrene), divinylbenzene, butyl acetate, and benzoyl peroxide was injected into a dispersed phase for forming particles, and a 3% aqueous solution of polyvinyl alcohol was injected into a microsyringe into a continuous phase, and liquid was sent. The liquid sending flow rate is 6 μl / min for both the dispersed phase and the continuous phase. Observing the junction where the dispersed phase and continuous phase of the microchannel structure for particle generation intersect in a state where the flow rates are both stable, particle generation can be confirmed, but separation and coalescence occurs in the discharge channel, When the generated particles (the generated particles 23 and the like) are observed, as shown in FIG. 8, the generated particles include not only particles having a particle diameter of about 70 μm but also particles having a small particle diameter. It was bad. In the case of producing droplets having good dispersibility with the microchannel structure for producing droplets having this aspect ratio, the flow rate of the liquid should be set to a continuous phase> disperse phase, specifically, a flow rate ratio of 5: 1 or more. It is necessary to feed the continuous phase in excess.
(Comparative Example 2)
FIG. 9 shows a microchannel for particle production in Comparative Example 2. As in Example 2, the microchannels were formed on polyetherimide of 70 mm × 20 mm × 1 t (thickness), and the width of the continuous phase introduction channel 3, the dispersed phase introduction channel 5, and the discharge channel 7 were all 140 μm. Y having a depth of 60 μm and a microchannel having an aspect ratio of 0.43, and having a junction where the continuous phase introduction channel 3 and the dispersed phase introduction channel 5 intersect at an angle of 44 degrees. One U-shaped channel was formed. Using the same photomask and technique as those described in Example 1, a flow path was formed on a 200 mm diameter Pyrex (registered trademark) glass substrate, a Ni thin film was formed, and a 300 μm thick film was formed by electroplating. A stamper was prepared and set in a mold of a molding machine, and a polyetherimide resin was prepared by an injection molding method. The prepared channel substrate was cut out at 70 mm × 20 mm × 1 t.
[0034]
Next, as shown in FIG. 10, the microchannel structure for particle production is held by a holder, and fixed and connected to a Teflon (registered trademark) tube, a fillet joint, and a micro syringe pump. A mixed solution of a monomer (styrene), divinylbenzene, butyl acetate, and benzoyl peroxide was injected into a dispersed phase for forming particles, and a 3% aqueous solution of polyvinyl alcohol was injected into a microsyringe into a continuous phase, and liquid was sent. The liquid sending flow rate is 6 μl / min for both the dispersed phase and the continuous phase. When the junction where the dispersed phase and the continuous phase of the microchannel structure for particle production intersect was observed in a state where the flow rates were both stable, laminar flow was observed without confirming the particle formation phenomenon. Further, the flow rate of the continuous phase was increased to make it easy to form particles.
[0035]
【The invention's effect】
The present invention has the following effects.
(1) The method for producing particles according to the present invention is capable of producing extremely uniform particles and also capable of controlling the particle diameter.
(2) Since the microchannel structure of the present invention can produce particles without depending on the channel material, the cost of the apparatus can be reduced by using a resin microchannel.
(3) Since the microchannel structure of the present invention has excellent particleization stability and can increase the flow rate of the dispersed phase, a large amount of particles can be produced in a short time and can be used industrially. It is.
(4) The microchannel structure according to the present invention can be used without changing the width and depth of the microchannel in the particle production method, the flow rate of the dispersed phase to be introduced, and the flow rate of the continuous phase. By changing only the angle of the confluence, it is possible to control the produced particle diameter.
(5) The microchannel structure of the present invention merges with the dispersed phase channel when the angle at which the introduction channel for introducing the dispersed phase intersects with the introduction channel for introducing the continuous phase is less than 90 degrees. By locally narrowing the width of the continuous phase flow path outlet or the discharge flow path inlet at the intersection of the two flow paths, and when the intersection angle is 90 degrees or more, the combination of the intersection angle and the flow velocity is adjusted. This makes it possible to stabilize the particle generation location in the vicinity of the confluence, and to stably produce the particles.
[Brief description of the drawings]
FIG. 1 is a schematic view showing a general microchannel for producing particles.
FIG. 2 is a schematic view showing a microchannel structure for producing fine particles used in Example 1.
FIG. 3 is a flowchart showing a method for forming a microchannel for producing fine particles in Example 1.
FIG. 4 is a schematic view showing a microchannel structure for producing fine particles used in Examples 1 and 2.
FIG. 5 is a schematic view showing a microchannel structure for producing fine particles and a pump connection used in Examples 1 and 2.
FIG. 6 is a photograph showing generated particles in Example 1.
FIG. 7 is a photograph showing generated particles in Example 2.
FIG. 8 is a photograph showing generated particles in Comparative Example 1.
FIG. 9 is a schematic view showing a microchannel structure for producing fine particles in Comparative Examples 1 and 2.
FIG. 10 is a schematic view showing a microchannel structure for producing fine particles and pump connection in Comparative Examples 1 and 2.
FIG. 11 is a schematic diagram showing a microparticle generation microchannel structure having a narrow channel width at a continuous phase channel outlet or a discharge channel inlet at the intersection of both channels used in Example 3. .
FIG. 12 is a photograph showing generated particles in Example 3. FIG. 13 is a schematic diagram showing a microchannel structure for fine particle generation when a continuous phase intersects a dispersed phase at an angle of 90 ° or more. .
[Explanation of symbols]
1: microchannel substrate 2: continuous phase inlet 3: continuous phase inlet 4: disperse phase inlet 5: dispersed phase inlet 6: junction 7: outlet 8: outlet 9: glass substrate 10 : Metal film 11: Photoresist 12: Photomask 13: Substrate with microchannel formed 14: Cover 15: Microchannel structure 16: Holder 17: Beaker 18: Teflon (registered trademark) tube 19: Fillet joint 20: Micro syringe pump 21: Micro syringe (continuous phase)
22: micro syringe (dispersed phase)
23: Produced particles 24: Protrusion-like structure provided at continuous phase channel outlet or discharge channel inlet 25: Generated particles

Claims (18)

While continuously introducing the dispersed phase and two or more continuous phases into a structure having a microchannel, the dispersed phase is brought into contact with the continuous phase, and the dispersed phase is sheared into fine particles. Particle production method. The method for producing particles according to claim 1, wherein the two or more continuous phases have the same composition. An introduction port for introducing the dispersed phase and an introduction flow path communicating therewith, an introduction port for introducing the continuous phase and an introduction flow path communicated therewith, and the particles generated by the dispersed phase and two or more continuous phases. A method for producing particles using a microchannel structure having a discharge channel including a microchannel for discharging and a discharge port communicating with the discharge channel, wherein the introduced dispersed phase and the continuous phase come into contact with each other. The method for producing particles according to claim 1 or 2, wherein the dispersed phase is made into fine particles at the junction. 4. The method according to claim 1, wherein the particle diameter of the generated particles is controlled by changing the angle at which the introduction flow path for introducing the dispersed phase and the introduction flow path for introducing the continuous phase intersect. Or a method for producing particles. The method for producing particles according to any one of claims 1 to 4, wherein the dispersed phase is a medium containing a raw material for producing a gel. The method for producing particles according to any one of claims 1 to 5, wherein the gel producing dispersant is polyvinyl alcohol. The method for producing particles according to any one of claims 1 to 6, wherein the continuous phase is a medium containing a dispersant for producing a gel. The method for producing particles according to claim 1, wherein the particles are droplets. An inlet for introducing the disperse phase and an inlet channel communicating therewith, two or more inlets for introducing the continuous phase and an inlet channel communicating therewith, formed by the disperse phase and two or more continuous phases And a discharge channel communicating with the discharge channel, the discharge channel comprising a microchannel for discharging the particles, and an aspect ratio (depth / width of the channel) of the cross section of the discharge channel. ) Is 0.30 or more. The introduction flow path for introducing the disperse phase and the two or more introduction flow paths for introducing the continuous phase intersect at an arbitrary angle, and the introduction flow path is connected to the discharge flow path at an arbitrary angle. The microchannel structure according to claim 9, wherein: 11. The microchannel structure according to claim 9, wherein an aspect ratio of a channel cross section is 0.30 or more and less than 3.0. The microchannel structure according to any one of claims 9 to 11, wherein the width of the introduction channel for introducing the dispersed phase and the width of the introduction channel for introducing the continuous phase are equal. The microchannel structure according to any one of claims 9 to 12, wherein, in the relationship between the width of the introduction channel and the width of the discharge channel, the width of the introduction channel ≥ the width of the discharge channel. . The width of the discharge flow path is reduced at a part of the discharge flow path from the intersection where the dispersed phase and the continuous phase intersect to the discharge port, wherein the width of the discharge flow path is narrowed. The microchannel structure according to the above. 15. The microchannel structure according to claim 14, wherein the portion where the width of the discharge channel is narrowed is at or near an intersection in the discharge channel. 16. The microchannel structure according to claim 14, wherein the portion where the width of the discharge channel is narrow is located at the intersection of the discharge channel and the flow channel side of the dispersed phase. A continuous phase flow path outlet or discharge flow path at a junction of a flow path having an intersection angle of less than 90 degrees and an upstream of the introduction flow path for introducing the dispersed phase and the introduction flow path for introducing the continuous phase being on the same side. The microchannel structure according to any one of claims 9 to 16, wherein the width of the channel at the inlet is narrowed, and control is performed such that the particle generation location is on the merging portion side. The microchannel structure according to any one of claims 9 to 17, wherein the particles are droplets.

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