JP5116334B2 - Method for producing highly monodisperse fine particles - Google Patents

Description

  The present invention relates to highly monodispersed fine particles and a method for producing the same. More specifically, the present invention relates to a method for producing a fine particle polymer having a nano-order particle size and a narrow particle size distribution.

Conventionally, suspension polymerization methods, emulsion polymerization methods, soap-free polymerization methods, seed polymerization methods, dispersion polymerization methods, and the like are known as methods for producing nano-order resin fine particles (for example, Patent Document 1).
However, since the particles produced by these polymerization methods have low monodispersity, they have problems as resin fine particles used in the medical and electronic materials fields.
On the other hand, a method for producing monodisperse resin fine particles using a microreactor is known (for example, Patent Document 2).
However, although the particle diameter of the fine particles greatly depends on the diameter of the microreactor, since the diameter of the microreactor is in the micron order, it is difficult to obtain monodispersed fine particles having a particle diameter in the nano order.
JP-A-5-222204 JP2001-181309

  The subject of this invention is providing the simple manufacturing method of the highly monodispersed resin microparticles | fine-particles which have the target particle size in nano order.

The inventor of the present invention has arrived at the present invention as a result of intensive studies on a method for producing nano-particles, which is highly monodisperse with a narrow particle size distribution.
The dispersed phase (D) containing the polymerizable monomer (b) is discharged from the connected opening to the continuous phase (B) flowing through the microreactor (A) and dispersed in the continuous phase (B). In the production method for producing monodisperse fine particles (I) by producing droplets (C ′) composed of the dispersed phase (D) and polymerizing them, the droplets (C ′) having a relatively large particle diameter are externally applied. By applying a uniform shearing force, a monodisperse fine particle (I) having an average particle diameter of 50 nm to 500 nm is obtained by making the liquid droplets (C) smaller and more monodispersed. This is a method for producing fine particles.

  When the production method of the present invention is used, monodispersed fine particles can be produced as compared with the conventional production method. Further, the particle diameter can be adjusted without depending on the tube diameter or groove width of the microreactor. In particular, it is possible to produce nano-order fine particles without extremely reducing the tube diameter and groove width of the microreactor.

  The material of the microreactor (A) is not particularly limited, and examples thereof include conventionally used inorganic materials such as glass, fluorescent glass, quartz, ceramics, and silicon. Of these, glass, quartz, and ceramics are more preferable. These inorganic materials have excellent chemical resistance and heat resistance, and can form micron-order grooves on a substrate by an optical lithography technique widely used in semiconductor processing technology.

Moreover, it is also possible to use a polymer resin in the above materials. These are not particularly limited, and examples of the thermoplastic resin include polyolefin resins, polystyrene resins, polylactic acid resins, polyacrylic resins such as polymethylmethacrylate, polycarbonate resins, and silicones such as polydimethylsiloxane. Resin, and polyolefin resin and polystyrene resin having acid resistance and alkali resistance are more preferable.

In addition to the above thermoplastic resins, thermosetting resins such as epoxy resins and phenol resins can be used from the viewpoint of cost and easy handling.

  Furthermore, the flow path diameter is not particularly limited as long as the fluid flowing through the microreactor can easily form a laminar flow and has a groove width. The tube diameter and groove width are preferably in the range of 1 μm to 1000 μm, and more preferably 1 μm to 600 μm.

Here, the laminar flow means that the flow line of the fluid is always parallel to the tube axis, and the contact frequency of particles in the environment is reduced. Therefore, the coalescence due to the contact of the particles is extremely difficult, so that the monodispersity of the obtained fine particles can be maintained. This laminar flow is generally considered to be laminar when the numerical value is 2100 or less at the Reynolds number Re, which is a representative parameter indicating the state of fluid flow. The Reynolds number Re is defined by the following mathematical formula.
Re = ud / ν
However, kinematic viscosity coefficient ν, flow velocity u, and pipe diameter d are represented.

The particle size and particle size distribution of the highly monodispersed fine particles (I) of the present invention can be measured by a particle size distribution measuring apparatus using electrophoretic light scattering.
Specifically, a solution obtained by concentrating the obtained particle solution with a circulating dryer or a micro vacuum dryer is analyzed with an electrophoretic light scattering particle size distribution measuring device (ELS), and from the analysis by the Marquad method, Obtain the average particle size and particle size distribution.

The average particle diameter of the monodispersed resin particles (I) of the present invention is preferably 50 to 500 nm, more preferably 100 to 500 nm, and still more preferably 200 to 500 nm.
The particle size distribution has a particle size variation coefficient (CV value) of preferably 10% or less, more preferably 8% or less, and still more preferably 5% or less.
Here, the variation coefficient of the particle size is a value calculated from the following calculation formula.
Coefficient of variation CV = (standard deviation / average particle size) × 100

In the production of the fine particles of the present invention, examples of the polymerizable monomer (b) applicable to the oil-in-water system include, for example, vinyl aromatic monomers, acrylic monomers, vinyl ester monomers, vinyl ether monomers. Body, diolefin monomer, monoolefin monomer and the like.
Examples of monovinyl aromatic monomers include monovinyl aromatic hydrocarbons such as styrene, α-methylstyrene, vinyltoluene, α-chlorostyrene, o-, m-, p-chlorostyrene, p-ethylstyrene, divinylbenzene. Or a combination of two or more thereof.
Examples of the acrylic monomer include methyl acrylate, ethyl acrylate, butyl acrylate, 2-ethylhexyl acrylate, cyclohexyl acrylate, phenyl acrylate, methyl methacrylate, hexyl methacrylate, and 2-ethylhexyl methacrylate. , Β-hydroxyethyl acrylate, γ-hydroxyacrylate propyl, δ-hydroxyacrylate butyl, β-hydroxymethacrylate ethyl, ethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, and the like.
Examples of vinyl ester monomers include vinyl formate, vinyl acetate, and vinyl propionate.
Examples of the vinyl ether monomer include vinyl methyl ether, vinyl ethyl ether, vinyl n-butyl ether, vinyl phenyl ether, vinyl cyclohexyl ether, and the like.
Examples of the diolefin monomer include butadiene, isobrene, chloroprene and the like.
Examples of the monoolefin monomer include ethylene, propylene, isobutylene, butene-1, pentene-1, 4-methylpentene-1, and the like.

The polymerizable monomer (b) may be diluted with an organic solvent or the like. The organic solvent used at this time is not particularly limited as long as the polymerizable monomer is soluble, and examples thereof include aliphatic hydrocarbons such as n-hexane and n-octane, and halogenated carbonization such as carbon tetrachloride. Examples thereof include aromatic hydrocarbon solvents such as hydrogen, toluene and xylene.

  In the production of the fine particles of the present invention, examples of the polymerizable monomer (b) applicable to the water-in-oil system include ethylenically unsaturated carboxylic acid amides such as acrylamide, methacrylamide, fumaramide, and ethacrylamide, and amino acids of unsaturated carboxylic acids. Examples thereof include water-soluble polymerizable monomers such as alkyl esters and acid anhydrides, ethylenically unsaturated carboxylic acids such as acrylic acid and methacrylic acid.

  At this time, examples of the continuous phase (B) of the water-in-oil system include aliphatic hydrocarbons such as n-hexane and n-octane, halogenated hydrocarbons such as carbon tetrachloride, toluene, xylene and the like. Aromatic hydrocarbon solvents are used.

  The water-soluble initiator (c) used in the emulsion polymerization of the present invention is preferably a free radical initiator. Not particularly limited, for example, hydrogen peroxide, acetyl peroxide, cumyl peroxide, tert-butyl peroxide, propionyl peroxide, benzoyl peroxide, chlorobenzoyl peroxide, dichlorobenzoyl peroxide, bromomethyl peroxide Benzoyl, lauroyl peroxide, ammonium persulfate, sodium persulfate, potassium persulfate, diisopropyl peroxycarbonate, tetralin hydroperoxide, 1-phenyl-2-methylpropyl-1-hydroperoxide, tert-butyl hydroperoxide pertriphenylacetate, Tert-butyl formate, tert-butyl peracetate, tert-butyl perbenzoate, tert-butyl perphenyl acetate, tert-butyl permethoxyacetate, tert-butyl per-N- (3-toluyl) carbamate, anhydrobisulfate Chloride, sodium bisulfate, peroxides, etc. and the like. More preferred water-soluble initiators are persulfate initiators such as ammonium persulfate, potassium persulfate, sodium persulfate and the like. The free radical initiator is usually used as an aqueous solution in addition to the monomer emulsion and / or aqueous phase.

  The amount of the water-soluble initiator is usually about 0.1 to 10% by mass of the monomer to be polymerized, and the total amount of the water-soluble initiator used for preparing the polymer is added to the continuous phase.

  The oil-soluble initiator (d) used in the suspension polymerization of the present invention is not particularly limited, and can be used in combination with a commonly used organic peroxide polymerization initiator having radical polymerizability. . Examples of the organic peroxide polymerization initiator include di-t-butyl peroxide, t-butylcumyl peroxide, dicumyl peroxide, acetyl peroxide, isobutyl peroxide, octanonyl peroxide, decanonyl peroxide. , Lauroyl peroxide, 3,5,5-trimethylhexanoyl peroxide, benzoyl peroxide, m-toluoyl peroxide, t-butylperoxypivalate, t-butylperoxyisobutyrate, t-butylperoxy Neodecanoate, t-butylperoxy 3,5,5-trimethylhexanoate, t-butylperoxy 2-ethylhexanoate, t-butylperoxybenzoate, t-butylperoxyisopropyl carbonate, t- Butylpa Oxy 2-ethylhexyl carbonate, 2,2-bis (4,4-di -t- butyl peroxy cyclohexyl) propane, t- butyl peroxy acetate, and the like. Among these, from the viewpoint of sustaining the polymerization activity for the raw material monomer and shortening the polymerization time, octanonyl peroxide, decanonyl peroxide, lauroyl peroxide, benzoyl peroxide, m-toluoyl peroxide, t-butyl peroxide. Oxybenzoate, t-butyl peroxy 2-ethylhexanoate, t-butyl peroxy 2-ethylhexyl carbonate, t-butyl peroxyacetate, and t-butyl peroxyisopropyl carbonate are preferred.

  The amount of the oil-soluble initiator is usually 0.1 to 10% by mass of the monomer to be polymerized, and more preferably 0.2 to 5% by mass.

In the production of the fine particles of the present invention, the surfactant (a) and the like can be contained in the continuous phase (B) in order to stabilize the monomer droplets.
The surfactant (a) is not particularly limited. For example, anionic emulsifiers (sodium dodecylbenzenesulfonate, sodium lauryl sulfate, sodium alkyldiphenyl ether disulfonate, sodium polyoxyethylene alkyl ether sulfate, etc.) Nonionic emulsifier (polyoxyethylene alkylphenyl ether, polyoxyethylene alkyl ether, polypropylene glycol ethylene oxide adduct, etc.); Cationic emulsifier (stearylbenzyldimethylammonium chloride, distearylbenzyldimethylammonium chloride, etc.); Polymerizable emulsifier ( Such as sodium alkylallylsulfosuccinate, sodium (meth) acryloyl polyoxyalkylene sulfate, etc.) That. Two or more of these may be used in combination.
The amount of the surfactant (a) to be contained in the continuous phase (B) may be an amount that does not inhibit the present invention, and is generally a small amount, specifically 0.01 to 10% by weight. , Preferably 0.05 to 5% by weight.

Furthermore, when performing suspension polymerization, in the oil-in-water system, a stabilizer may be added to stabilize the monomer droplets. For example, water-soluble polymers such as polyvinyl alcohol, polyvinyl pyrrolidone, carboxymethyl cellulose, hydroxymethyl cellulose, starch, and gelatin; poorly water-soluble inorganic salts such as tricalcium phosphate and the like can be contained in the continuous phase (B).
The amount of the stabilizer to be contained in the continuous phase (B) may be an amount that does not inhibit the present invention, is generally a small amount, specifically 0.01 to 10% by weight, preferably 0.05 to 5% by weight.

  In the production of the fine particles of the present invention, a reducing agent (for example, sodium pyrobisulfite, sodium sulfite, sodium hydrogensulfate, ferrous sulfate, glucose, sodium formaldehyde sulfone) is used in the continuous phase (B) for particle stabilization. Xylates, L-ascorbic acid (salts, etc.), chelating agents (glycine, alanine, sodium ethylenediaminetetraacetate, etc.), pH buffers (sodium tripolyphosphate, potassium tetrapolyphosphate, etc.), sensitizers, viscosity modifiers, etc. These known additives may be included.

In the method for producing monodisperse fine particles according to the present invention, the shear force generated by the flow of the continuous phase of the microreactor is applied to the droplet (C ′) dispersed in the continuous phase prepared in advance to further apply a microscopic force from the outside. After forming into droplets (C), this is polymerized to obtain particles having an average particle diameter of 50 nm to 500 nm. The method of applying a shearing force from the outside at this time includes operations usually used for this purpose. Equipment etc. can be used.
For example, a dispersion method using ultrasonic energy, acoustic energy generated by low-frequency vibration, a micromixer that stirs and mixes and disperses the microreactor by making it a multi-stage collision type, and a minute phase by passing the dispersed phase through a porous membrane. Examples thereof include a method of forming droplets. A method of dispersing by ultrasonic irradiation, low-frequency vibration, and permeation of a porous membrane is preferable, and ultrasonic irradiation is particularly preferable.
By performing these in a microreactor, it is possible to prevent a wide distribution in the shearing force and to provide uniform shearing. Therefore, a monodispersed microfluid smaller than the microreactor tube diameter and groove width. Drops (C) can be made.

The ultrasonic irradiation energy may be any energy that can mix and disperse the solvent in the microreactor. Then, the irradiation energy of the ultrasonic wave, usually ^{1.0 × 10 5 W / m 3} ~1.0 × 10 9 W / m 3, ^{preferably, 1.0 × 10 7 W / m} 3 ~1.0 × 10 ⁹ W / m ³ .
Specifically, the monomer droplets are miniaturized by irradiating ultrasonic waves to the site where the monomer droplets are produced from the openings in the microreactor.
Furthermore, fine droplets having a desired particle diameter can be obtained by adjusting the irradiation energy at this time.

As described above, microdroplets in an environment where a laminar flow is formed reduce the frequency of mutual contact with each other, so coalescence due to particle contact is extremely difficult to occur. It is possible to maintain monodispersity.
In addition, as a means for controlling particle contact other than laminar flow, it is possible to reduce the contact frequency between particles by applying a magnetic field to the microreactor to form a pseudo-gravity field. These can be used in combination.

  The formation of such a pseudo-gravity field is not particularly limited as long as it generates a magnetic field. For example, an electromagnet, a hybrid magnet, and the like can be used, and these can be used in combination. Specifically, an electromagnet is installed in the microreactor channel so that a magnetic field is applied from below. The strength of the magnetic field varies depending on the solvent and medium used for the reaction, but preferably a magnetic field of 10T to 25T can be applied.

The highly monodispersed fine particles (I) are obtained by polymerization of the fine droplets (C), and the reaction temperature at that time is usually 35 to 150 ° C. Preferably it is 60-90 degreeC, More preferably, it is 80 degreeC-90 degreeC.
The heat source used for the reaction may be a commonly used one, and examples thereof include heating by an oil bath or water bath, heating by microwave irradiation, etc., preferably heating by microwave irradiation.

  In addition, when the droplet flowing through the microreactor is heated, since the volume of the microreactor is small, the heat energy by heating can be instantaneously and uniformly given to the droplet. For this reason, the degree of polymerization of the monomers can be made uniform, and a polymer having a narrow molecular weight distribution can be obtained.

  The molecular weight and molecular weight distribution of the monodispersed resin particles (I) of the present invention can be measured by gel permeation chromatography (GPC) using several types of monodispersed polystyrene as standard samples.

The monodisperse resin particles (I) of the present invention have a weight average molecular weight (Mw) of 3000 to 1 million, preferably 5000 to 500,000. The molecular weight distribution (weight average molecular weight Mw / number average molecular weight Mn) is 1.01-1.20, preferably 1.01-1.10.
Here, Mw represents a weight average molecular weight, and Mn represents a number average molecular weight.

The time required for the polymerization is usually about 0.5 to 8 hours, preferably 1 to 6 hours, and particularly preferably 1 to 4 hours.

EXAMPLES Hereinafter, although an Example demonstrates this invention further, this invention is not limited to this.
Example 1
A glass microreactor having a channel width of 400 μm was prepared as a reaction field.
As for the continuous phase, 1331 parts by weight of distilled water and 5.3 parts by weight of nonionic surfactant Eleminol NL-100 (polyoxyethylene alkyl ether manufactured by our company) are added in advance, and nitrogen gas is blown into water and dissolved in water. Oxygen was replaced over about 1 hour. A solution obtained by dissolving 6.15 parts by weight of potassium persulfate as a water-soluble initiator in 170 parts by weight of water was added to obtain a continuous phase. A styrene monomer was used for the dispersed phase.
The liquid was fed at a continuous phase flow rate of 20 ml / hr and a dispersed phase flow rate of 1 ml / hr. The droplets were miniaturized by applying a low frequency vibration of 30 Hz for 1 minute by a small vibration motor device to the site where both liquids were in contact with each other to produce a dispersion. This dispersion was instantaneously heated to 85 ° C. by microwave irradiation and held for 1 hour to conduct a polymerization reaction.
A part of the obtained particle solution was dried for 1 hour with a 60 ° C. normal air dryer, concentrated, and measured with an electrophoretic light scattering particle size distribution analyzer (ELS). As a result, an average particle size of 290 nm and a CV value of 3. 9% highly monodispersed fine particles were obtained. Further, the fine particles had Mw = 13940 and Mw / Mn = 1.09 as measured by GPC.

Example 2
Particles were obtained in the same manner as in Example 1 except that the flow path width was 40 μm and the flow rate of the continuous phase was 5 ml / hr. As a result, highly monodispersed fine particles having an average particle diameter of 185 nm, a CV value of 4.7%, Mw = 125010, and Mw / Mn = 1.08 were obtained.

Example 3
Particles were obtained in the same manner as in Example 1 except that the initiator was lauroyl peroxide, which is an oil-soluble initiator. As a result, highly monodispersed fine particles having an average particle size of 220 nm, a CV value of 4.1%, Mw = 18740, and Mw / Mn = 1.16 were obtained.

Example 4
Particles were obtained in the same manner as in Example 1 except that the channel width was 100 μm and the flow rate of the continuous phase was 3 ml / hr. As a result, monodispersed fine particles having an average particle diameter of 215 nm, a CV value of 7.2%, Mw = 15460, and Mw / Mn = 1.11.

Comparative Example 1
Particles were obtained in the same manner as in Example 1 except that a microreactor having a channel width of 400 μm was used and no low-frequency vibration was applied. As a result, fine particles having an average particle size of 288 μm, a CV value of 4.9%, Mw = 14190, and Mw / Mn = 1.13 were obtained. Since the average particle size of the fine particles obtained here could not be measured by ELS, a laser diffraction / scattering particle size distribution measuring device was used.

Comparative Example 2
Particles were obtained in the same manner as in Comparative Example 1 with no low frequency vibration except that the channel width was 40 μm. As a result, fine particles having an average particle size of 24 μm, a CV value of 7.8%, Mw = 12720, and Mw / Mn = 1.09 were obtained.

  From the above results, the fine particles obtained in Examples 1 to 4 were all highly monodispersed with a nano-order particle size smaller than the channel width and a variation coefficient of 10% or less. On the other hand, in Comparative Examples 1 and 2, it can be seen that only micron-sized particles corresponding to the set channel width can be obtained.

When the production method of the present invention is used, highly monodisperse resin fine particles having a target particle size in the nano order can be easily produced as compared with the conventional production method. Highly monodispersed resin fine particles produced in this way are used in the fields of medical materials and electronic materials.

Claims (9)

  The dispersed phase (D) containing the polymerizable monomer (b) is discharged from the connected opening to the continuous phase (B) flowing through the microreactor (A) and dispersed in the continuous phase (B). In the production method for producing monodisperse fine particles (I) by producing droplets (C ′) composed of the dispersed phase (D) and polymerizing them, a uniform shearing force is applied to the droplets (C ′) from the outside. A monodispersed fine particle (I) having an average particle size of 50 nm to 500 nm is obtained by adding monodispersed fine droplets (C) by adding a high-dispersed fine particle.   The method for producing highly monodispersed fine particles according to claim 1, wherein the continuous phase (B) contains a surfactant (a).   The method for producing highly monodispersed fine particles according to claim 1 or 2, wherein the polymerization is emulsion polymerization using a water-soluble initiator (c).   The method for producing highly monodispersed fine particles according to claim 1 or 2, wherein the polymerization is suspension polymerization using an oil-soluble initiator (d).   The method for producing highly monodispersed fine particles according to any one of claims 1 to 4, wherein the shearing force is due to irradiation with ultrasonic waves. 6. The method for producing highly monodispersed fine particles according to claim 5, wherein the irradiation energy of the ultrasonic waves is 1.0 × 10 ⁷ W / m ^{3 to} 1.0 × 10 ⁹ W / m ³ .   The method for producing highly monodispersed fine particles according to any one of claims 1 to 6, wherein the fine droplets (C) are dispersed in the continuous phase (B).   The method for producing highly monodispersed fine particles according to any one of claims 1 to 7, wherein the coefficient of variation CV of the particle size distribution of the highly monodispersed fine particles (I) is 10% or less. The method for producing highly monodispersed fine particles according to any one of claims 1 to 8, wherein the diameter of the microreactor (A) is 1 µm to 1000 µm.