JP5358241B2 - Method for producing vinyl polymer particles and vinyl polymer particles - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method suitable for producing vinyl polymer particles: hardly causing discoloration due to falling-off of a fluorescent dye when applied to uses such as a tracer for a fluid-visualization device, standard particles for precision control of flow cyto and a carrier for immunity diagnostic agent; encapsulating a water-soluble fluorescent dye; and having a more fine particle diameter compared with conventional particles, and to provide vinyl polymer particles suitable for use in a scaled-down micro fluid device. <P>SOLUTION: This method for producing the vinyl polymer particles includes polymerizing a vinyl monomer by dispersing the vinyl monomer and a water-soluble fluorescent dye into an aqueous medium to produce the vinyl polymer particles containing the water-soluble fluorescent dye. The polymerization is carried out by emulsion polymerization of the vinyl monomer in the presence of a surface active agent and a polymerization initiator. The emulsion polymerization is performed by dispersing the vinyl monomer having a carboxyl group and the vinyl monomer having a functional group bondable with the carboxyl group of the vinyl monomer in the aqueous medium. <P>COPYRIGHT: (C)2011,JPO&amp;INPIT

Description

  The present invention relates to a method for producing vinyl polymer particles containing a water-soluble fluorescent dye and vinyl polymer particles.

  Currently, fine particles that emit fluorescence are widely used in various fields. Among them, they play an important role as fluid tracer tracers, flow-site quality control standard particles, and immunodiagnostic drug carriers. As the particle size to be used, those of several μm to several hundreds of μm are the mainstream due to the shape of use and visibility, but in recent years it has a smaller particle size in the submicron region as the microfluidic device scales down. There is a strong demand for fluorescent particles.

Conventionally, as a method for producing such fluorescent fine particles,
(1) A method of dyeing polymer particles by immersing them in a fluorescent dye bath,
(2) After forming a layer having a functional group that reacts with a fluorescent dye on the surface of the polymer particles, a method of dyeing by immersing in a fluorescent dye bath (for example, US Pat. No. 4,774,189 (the following Patent Document 1) and US Pat. No. 5,194,300 (described in Patent Document 2 below),
(3) Method of forming phosphor (fluorescent dye) -containing resin particles by suspension polymerization in which a monomer composition in which a phosphor or fluorescent dye is added to a monomer is dispersed in a medium and polymerization is performed, and the phosphor and fluorescent pigment used And a surface treatment method for improving the dispersibility of the fluorescent dye in the monomer composition (for example, described in JP-A-9-176366 (Patent Document 3 below)),
(4) A method for obtaining water-soluble fluorescent dye-containing resin particles by suspension polymerization using a water-soluble fluorescent dye and a vinyl monomer having a functional group that binds to the water-soluble fluorescent dye (for example, JP 2006-2006 A). -265401 (described in Patent Document 4 below),
Etc. are known.

U.S. Pat. No. 4,774,189 US Pat. No. 5,194,300 JP-A-9-176366 JP 2006-265401 A

However, each of the above methods has the following problems.
Although the method (1) is a very simple production method as a dyeing method, it is based on physical adsorption to the surface layer, and it is difficult to fix the fluorescent dye.
In the method (2), in addition to the production steps generally required to produce polymer particles, a layer having a functional group that reacts with a dye is formed on the surface of the polymer particles, and then a fluorescent dye bath is used. The manufacturing process is complicated because the dyeing process is necessary, and the fluorescent dye is gradually used when the particles are used, although not as much as the particles obtained by the manufacturing method (1) for dyeing only the surface layer. There was a problem of deviating and fading.
Furthermore, the production methods of (1) and (2) both require a fluorescent dye bath. As a common problem, the use efficiency of the fluorescent dye is very poor, and washing is repeated when unnecessary fluorescent dyes are washed away. The process is complicated and time consuming. Furthermore, there was a risk of increasing the environmental load in wastewater treatment and the like.

Therefore, the present inventor tried to obtain vinyl polymer particles uniformly containing a water-soluble fluorescent dye by the methods (3) and (4).
Specifically, the fluorescent white dye (Ciba Geigy, Ubitex OB, hydrophobic fluorescent dye) of Example 2 of JP-A-9-176366 was changed to rhodamine B which is a water-soluble dye, and polymerization was attempted. B was hardly dissolved in the polymerizable composition of styrene as the polymerizable vinyl monomer and divinylbenzene as the cross-linking agent, and therefore it was not possible to obtain good water-soluble fluorescent dye-containing resin particles.

Next, vinyl polymer particles encapsulating a water-soluble fluorescent dye were produced based on the examples of JP-A-2006-265401.
At this time, an attempt was made to obtain vinyl polymer particles having an average particle diameter of 0.01 to 2 μm by changing the conditions of the stirring amount, the addition amount of the acidic organic modified phosphoric acid compound, the surfactant and the like. However, the intended fine particle size could not be obtained.
Furthermore, based on the composition of the examples in JP-A No. 2006-265401, the average particle diameter is 0.01 to 2 μm by an emulsion polymerization method that is generally known to facilitate the reduction in particle size. I tried to obtain vinyl polymer particles encapsulating water-soluble fluorescent dyes, but gelled in a state containing an aqueous dispersion medium and the whole system hardened, or a slurry-like high viscosity containing many lumps of resin. As a result, it was not possible to obtain particles having a target average particle diameter of 0.01 to 2 μm.

  In view of the above problems, the present invention suppresses a fading change due to deviation of a fluorescent dye when used in, for example, a tracer for a fluid visualization device, a standard particle for flow site accuracy control, a carrier for an immunodiagnostic drug, and the like. In addition, the present invention provides a production method suitable for the production of vinyl polymer particles encapsulating a water-soluble fluorescent dye having a finer particle size than conventional ones, and can be applied to scaled-down microfluidic devices and the like. An object is to provide vinyl polymer particles suitable for use.

  As a result of intensive studies to solve the above problems, the present inventor successfully dissolved a water-soluble fluorescent dye in a polymerizable monomer composition by using a vinyl monomer having a carboxyl group. Can be present uniformly and stably, and by polymerizing the vinyl monomer in such a system, vinyl polymer particles in which outflow of the water-soluble fluorescent dye to the aqueous dispersion medium is suppressed can be formed. Found to get.

  Moreover, when a polymerizable monomer composition is emulsion-polymerized in an aqueous dispersion medium by using a vinyl monomer having a functional group bonded to a carboxyl group in combination with a vinyl monomer having a carboxyl group. However, it has been found that vinyl polymer particles having a finer particle diameter than that of the conventional one can be obtained without causing gelation of the entire system. Furthermore, during production, the outflow to the aqueous dispersion medium is suppressed, so that the environmental load is very small.

That is, the present invention relating to a method for producing vinyl polymer particles is characterized in that the water-soluble fluorescent dye is obtained by polymerizing the vinyl monomer by dispersing a vinyl monomer and a water-soluble fluorescent dye in an aqueous medium. A vinyl polymer particle production method for producing a vinyl polymer particle containing a polymer, wherein the vinyl polymer particle to be produced has an average particle diameter of 0.01 to 2 μm, and the polymerization Is emulsion polymerization carried out in the presence of a surfactant and a polymerization initiator, and as the vinyl monomer, a vinyl monomer having a carboxyl group and the carboxyl group of the vinyl monomer A vinyl monomer having a functional group capable of binding to the aqueous medium is dispersed in the aqueous medium to carry out the emulsion polymerization, and the vinyl monomer in the emulsion polymerization has a carboxyl group. Simple quantity Is characterized by for causing the contained in a proportion of 20% by weight to 40% by weight.

Further, the present invention relating to vinyl polymer particles may contain the water-soluble fluorescent dye by dispersing a vinyl monomer and a water-soluble fluorescent dye in an aqueous medium and polymerizing the vinyl monomer. Vinyl polymer particles comprising:
The polymerization is an emulsion polymerization performed in the presence of a surfactant and a polymerization initiator, and the emulsion polymerization includes a vinyl monomer having a carboxyl group as the vinyl monomer, and the vinyl The vinyl monomer having a functional group capable of binding to the carboxyl group of the monomer is dispersed in the aqueous medium, and the vinyl monomer having a carboxyl group is contained in the vinyl monomer. characterized in that the average particle size by Rukoto the emulsion polymerization is contained is carried out mer in an amount of 20% by weight to 40% by weight is formed to be one of the 0.01~2μm It is said.

According to the present invention, the vinyl polymer particles in which the outflow of the water-soluble fluorescent dye to the aqueous dispersion medium is formed. For example, the fluid visualization device tracer, the flow site quality control standard particles, the immunity Vinyl polymer particles in which a fading change due to a deviation from a fluorescent dye during use in a carrier for a diagnostic agent or the like is suppressed can be produced.
Moreover, since vinyl polymer particles are prepared by emulsion polymerization in a state where the vinyl monomer is prevented from gelling in an aqueous medium, finer vinyl polymer particles are produced than before. Can be done.

  The vinyl polymer particles encapsulating the water-soluble fluorescent dye thus obtained and formed in a state where the average particle diameter is any one of 0.01 to 2 μm, It can be suitably used for a scaled-down microfluidic device or the like.

That is, according to the present invention, the change in fading due to the deviation of the fluorescent dye is suppressed, and moreover, the production of vinyl polymer particles encapsulating a water-soluble fluorescent dye having a finer particle size than conventional ones. A suitable manufacturing method can be provided.
Moreover, according to the present invention, vinyl polymer particles suitable for use in a scaled-down microfluidic device or the like can be provided.

The figure which shows the vinyl polymer particle of Example 1 (SEM photograph).

The vinyl polymer particles of the present invention and the method for producing vinyl polymer particles will be described.
First, the vinyl polymer particles of this embodiment will be described.

The vinyl polymer particles of the present embodiment contain the water-soluble fluorescent dye by dispersing a vinyl monomer and a water-soluble fluorescent dye in an aqueous medium and polymerizing the vinyl monomer. Vinyl polymer particles.
Moreover, the vinyl polymer particles of the present embodiment are emulsion polymerization in which the polymerization is performed in the presence of a surfactant and a polymerization initiator, and the emulsion polymerization has a carboxyl group as the vinyl monomer. And a vinyl monomer having a functional group capable of binding to the carboxyl group of the vinyl monomer is dispersed in the aqueous medium to carry out 0.01. It is formed to have an average particle diameter of any one of ˜2 μm.

The vinyl monomer having a carboxyl group is a component useful for incorporating a water-soluble fluorescent dye into the vinyl polymer particles, and a vinyl having a functional group that reacts with the carboxyl group of the vinyl monomer. The system monomer is contained as a crosslinking component for crosslinking polymers formed by polymerization.
For example, a vinyl monomer having a carboxyl group is polymerized to form a polymer having a carboxyl group in the side chain, and a vinyl monomer having a functional group capable of binding to the carboxyl group is polymerized. As a result, a polymer having a functional group that can be bonded to a carboxyl group in the side chain is formed, and these carboxyl groups are bonded to the functional group that can be bonded to the carboxyl group, thereby cross-linking between the polymers. To be implemented.
Hereinafter, the term “polymerizable vinyl monomer” will be used to refer to the vinyl monomer having a carboxyl group, and a vinyl monomer having a functional group that reacts with the carboxyl group of this “polymerizable vinyl monomer”. The present invention will be described using the term “crosslinking component” as a term indicating a monomer.

Among the components used to form the vinyl polymer particles of the present embodiment, examples of the polymerizable vinyl monomer (a vinyl monomer having a carboxyl group) include (meth) acrylic acid, 2- ( Mention of carboxylic acid-containing esters of (meth) acrylic acid such as (meth) acryloyloxyethyl succinic acid, 2- (meth) acryloyloxyethyl phthalic acid, 2- (meth) acryloyloxyethyl hexahydrophthalic acid Can do.
In the present specification, the term “(meth) acrylic acid” means “acrylic acid” or “methacrylic acid”.

The crosslinking component (a vinyl monomer having a functional group capable of binding to a carboxyl group) is a vinyl monomer having a functional group that binds to the carboxyl group of the preceding vinyl monomer by reaction. If it is, it will not specifically limit, As a specific example of the said crosslinking component, the (meth) acrylic acid ester which has a glycidyl group, the urethane (meth) acrylate containing a free isocyanate group, etc. can be mentioned.
Especially, as said functional group, a glycidyl group is suitable and it is preferable to use glycidyl (meth) acrylate as said crosslinking component.

The cross-linking component and the polymerizable vinyl monomer are usually emulsion polymerization so that the cross-linking component is in a proportion of 10 parts by weight or more and 100 parts by weight or less with respect to 100 parts by weight of the polymerizable vinyl monomer. It is preferable to be used for.
It is preferable that the cross-linking component is within the above range. When the amount is less than 10 parts by weight, the vinyl polymer is likely to agglomerate particles during the growth process of the vinyl polymer particles in the emulsion polymerization. This is because the particles may contain a large amount of coarse aggregated particles.
On the other hand, the reason why the upper limit of the preferable range is 100 parts by weight is that it is difficult to expect an effect commensurate with the increase in the proportion even if the proportion exceeds 100 parts by weight.
In this respect, the ratio of the crosslinking component to 100 parts by weight of the polymerizable vinyl monomer is more preferably 20 parts by weight or more and 70 parts by weight or less.

  Also, other vinyl monomers other than the polymerizable vinyl monomer and the crosslinking component can be used alone or in combination of two or more in a range not significantly impairing the effects of the present invention.

Other vinyl monomers are not particularly limited, and various commonly used vinyl monomers can be used.
For example, styrene, o-methylstyrene, m-methylstyrene, p-methylstyrene, p-ethylstyrene, 2,4-dimethylstyrene, pn-butylstyrene, p-tert-butylstyrene, pn-hexyl Styrene, pn-octyl styrene, pn-nonyl styrene, pn-decyl styrene, pn-dodecyl styrene, n-methoxy styrene, p-phenyl styrene, p-chloro styrene, 3,4-di Styrene and its derivatives such as chlorostyrene; vinyl halides such as vinyl chloride, vinylidene chloride, vinyl bromide, vinyl fluoride; vinyl esters such as vinyl acetate, vinyl propionate, vinyl benzoate, vinyl butyrate; ) Methyl acrylate, ethyl (meth) acrylate, n-butyl (meth) acrylate, (meth Isobutyl acrylate, propyl (meth) acrylate, n-octyl (meth) acrylate, dodecyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, stearyl (meth) acrylate, 2- (meth) acrylate 2- Α-methylene aliphatic monocarboxylic acid esters such as chloroethyl, phenyl (meth) acrylate, dimethylaminoethyl (meth) acrylate, diethylaminoethyl (meth) acrylate; (meth) acrylonitrile, (meth) acrylamide (meth) ) Acrylic acid derivatives can also be used.

  In addition, vinyl ethers such as vinyl methyl ether, vinyl ethyl ether, vinyl isobutyl ether; vinyl ketones such as vinyl methyl ketone, vinyl hexyl ketone, methyl isopropenyl ketone; N-vinyl pyrrole, N-vinyl carbazole, N-vinyl indole, N-vinyl compounds such as N-vinylpyrrolidone; vinyl naphthalene salts and the like can also be used as other vinyl monomers.

  Furthermore, polyfunctional polymerizable monomers such as divinylbenzene and alkylene glycol dimethacrylate (alkylene preferably has 2 to 4 carbon atoms) can also be used as other vinyl monomers.

  The other vinyl-based monomer and the polymerizable vinyl-based monomer used for forming the vinyl-based polymer particles in the present embodiment are usually other vinyl-based with respect to 100 parts by weight of the polymerizable vinyl-based monomer. A monomer can be used for the said emulsion polymerization in the ratio used as 30-1500 weight part.

When the ratio of the other vinyl monomer to 100 parts by weight of the polymerizable vinyl monomer is less than 30 parts by weight, the stability of the particles of the vinyl monomer mixture during the polymerization may be lowered, and there is a large amount of aggregates after the polymerization. There is a risk of containing vinyl polymer particles.
On the other hand, if the proportion exceeds 900 parts by weight, the proportion of the polymerizable vinyl monomer (vinyl monomer containing a carboxyl group) in the whole is reduced, resulting in water solubility in the vinyl monomer mixture during polymerization. There is a possibility that the fluorescent property of the vinyl polymer particles obtained may be lowered because the amount of the fluorescent dye dissolved is not sufficient.
For this reason, the ratio of the other vinyl monomer to 50 parts by weight with respect to 100 parts by weight of the polymerizable vinyl monomer is 50 to 900 parts by weight in order to form homogeneous vinyl polymer particles excellent in fluorescence. It is preferable that the emulsion polymerization is carried out at a mixing ratio.

The water-soluble fluorescent dye contained in the vinyl polymer particles formed by such a vinyl monomer can be dissolved almost uniformly in the polymerizable vinyl monomer and the carboxyl of the polymerizable vinyl monomer. There are no particular limitations as long as they are well bonded to the group, and examples thereof include rhodamine dyes such as rhodamine B and rhodamine 6G, stilbene dyes, fluorescein derivatives such as methylene blue, fluorescein, uranin and erythrosine.
Of these, rhodamine dyes such as rhodamine B and rhodamine 6G can be preferably used.

The amount of the water-soluble fluorescent dye used depends on the type of the water-soluble fluorescent dye used, but is based on 100 parts by weight of the polymerizable vinyl monomer (a vinyl monomer containing a carboxyl group). Thus, it is preferably used for emulsion polymerization at a ratio of 0.005 to 20 parts by weight, and more preferably 0.01 to 10 parts by weight.
It is preferable that the ratio of the water-soluble fluorescent dye is in the above range. If the ratio of the water-soluble fluorescent dye is less than 0.005 parts by weight, the resulting vinyl polymer particles may not have sufficient fluorescence. On the other hand, even if it is added in a proportion exceeding 20 parts by weight, it is difficult to expect an effect commensurate with the increase in the amount added.
Furthermore, when it is added in a proportion exceeding 20 parts by weight, there is a possibility that precipitation of undissolved material and polymerization inhibition of the vinyl monomer may occur.

In addition, it is also possible to contain components other than those described above in the vinyl polymer particles as long as the effects of the present invention are not significantly impaired, and other additives may be added.

  Examples of other additives include coloring components (coloring agents) other than water-soluble dyes, light stabilizers, ultraviolet absorbers, heat stabilizers, leveling agents, and antistatic agents.

  A composition containing components for constituting such vinyl polymer particles (hereinafter also referred to as “polymerizable monomer composition”) is present in an aqueous medium in the presence of a surfactant and a polymerization initiator. It is subjected to emulsion polymerization and used to form vinyl polymer particles.

The surfactant is not particularly limited, and an anionic surfactant, a cationic surfactant, a zwitterionic surfactant, and a nonionic surfactant that are usually used in the field are suitably used. Can do.
These surfactants may be reactive surfactants having a binding functional group that is reactive with vinyl monomers, or may not exhibit such reactivity.

  For example, reactive surfactants include alkenyl benzene sulfonates such as sodium styrene sulfonate; (meth) acrylate sulfonates; alkenyl sulfonates such as sodium vinyl sulfonate; allyl alkyl itaconate sulfate, etc. And polyoxyethylene (or propylene) alkenyl (phenyl) ether derivatives.

  For example, non-reactive surfactants include fatty acid oils such as sodium oleate and castor oil potassium; alkyl sulfate salts such as sodium lauryl sulfate and ammonium lauryl sulfate; alkylbenzene sulfonates such as sodium dodecylbenzenesulfonate; alkylnaphthalenes Examples include sulfonates, alkanesulfonates, dialkylsulfosuccinates, naphthalenesulfonic acid formalin condensates, polyoxyethylene alkylphenyl ether sulfates, polyoxyethylene alkyl sulfates.

These surfactants are different depending on their types, but are preferably used so as to have a ratio of 0.1 to 5 parts by weight with respect to 100 parts by weight of the polymerizable vinyl monomer.
It is more preferable to use so that it may become a ratio in any one of 0.3-3 weight part.

The polymerization initiator is not particularly limited, and those usually used in the field can be appropriately selected and employed.
Examples thereof include radical polymerization initiators and redox polymerization initiators that can cause radical decomposition by heat or radical decomposition by a reducing substance to initiate addition polymerization of a vinyl monomer.

  Examples of the radical polymerization initiator include 2,2-azobis (N-hydroxyethylisobutyramide), 2,2-azobis (2-amidinopropane) dichloride, 4,4-azobis (4-cyanopentanoic acid). Azo compounds such as potassium peroxodisulfate (KPS), sodium peroxodisulfate (NPS), peroxodisulfate such as ammonium peroxodisulfate (APS); hydrogen peroxide, t-butyl hydroperoxide, t-butyl Examples thereof include peroxides such as peroxymaleic acid, succinic acid peroxide, and benzoyl peroxide.

  Examples of the redox polymerization initiator include the above-mentioned peroxides, sodium sulfoxylate formaldehyde, sodium hydrogen sulfite, sodium thiosulfate, sodium hydroxymethanesulfinate, L-ascorbic acid and its salt, cuprous salt, first The combination with reducing agents, such as iron salt, is mentioned.

  These polymerization initiators are different depending on the kind thereof, but are preferably used in a proportion of 0.1 to 3 parts by weight with respect to 100 parts by weight of the polymerizable vinyl monomer.

The aqueous medium used for emulsion polymerization using such components is not particularly limited, and examples thereof include water, a mixture of water and a water-soluble organic solvent (for example, lower alcohol), and the like.
Among these, water is preferable in that the labor required for wastewater treatment can be reduced.

It is important that the vinyl polymer particles formed by these components have an average particle diameter of 0.01 to 2.0 μm.
For example, when the average particle diameter of the vinyl polymer particles containing the water-soluble fluorescent dye in this embodiment is less than 0.01 μm, it is necessary to use a large amount of a surfactant or an aqueous medium to obtain the particles, It becomes difficult to make it industrially suitable from the viewpoint of productivity.
On the other hand, when the average particle diameter exceeds 2.0 μm, it becomes difficult to satisfy the demand for fine particles.
Furthermore, those having an average particle diameter of more than 2.0 μm have the possibility of being able to be manufactured regardless of the manufacturing method described later.
That is, for example, vinyl polymer particles satisfy the demands for micronization as required in scaled-down microfluidic devices and the like, and can exhibit the effects of the present invention more remarkably. It is important that the average particle diameter is any one of 0.01 to 2.0 μm.
In addition, from these points, it is more preferable that the vinyl polymer particles of the present embodiment have an average particle diameter of 0.05 to 1.0 μm.
In addition, an average particle diameter can be calculated | required by the measuring method described in an Example.
In addition, the shape of the polymer particles obtained is not particularly limited, and may be spherical or non-spherical (flat, needle-like, indefinite shape...).

Next, a method for producing vinyl polymer particles will be described.
In the present embodiment, the production of vinyl polymer particles is carried out by emulsion polymerization performed by the components as described above.
The specific method for this emulsion polymerization is not particularly limited, and for example, after adding the polymerizable monomer composition, the surfactant, the polymerization initiator and the like in an aqueous medium, stirring is performed. There is a method in which an emulsion is formed, and then heated while stirring to obtain vinyl polymer particles containing a water-soluble dye.
The polymerization initiator may be added to the polymerization system after forming an emulsion.

  As a stirring method for forming this emulsion, a conventional method using a homogenizer or an ultrasonic disperser may be appropriately employed.

At this time, the ratio of the polymerizable monomer composition containing the polymerizable vinyl monomer, the crosslinking component, the water-soluble fluorescent dye, and other additives to the aqueous medium (polymerizable monomer composition: aqueous) The medium is preferably in the range of 1:20 to 1: 1 by weight ratio.
When the ratio of the polymerizable monomer composition is less than 1:20, the productivity of the vinyl polymer particles may be reduced.
On the other hand, when the ratio of the polymerizable monomer composition is more than 1: 1, the viscosity of the mixture of the polymerizable monomer composition and the aqueous medium becomes high and uniform polymerization may be difficult, There is a possibility that aggregates of polymer particles are generated.
Therefore, from the viewpoint of excellent productivity and more reliable production of fine and homogeneous vinyl polymer particles, the ratio of the use ratio of the polymerizable monomer composition to the aqueous medium in the emulsion polymerization is It is preferable that the ratio is any of 1:10 to 1: 3.

  Moreover, although superposition | polymerization temperature changes with kinds of the polymerizable monomer and polymerization initiator to be used, it is preferable that it is 30-100 degreeC, and it is preferable that superposition | polymerization time is 2 to 12 hours.

  By carrying out the emulsion polymerization under the above-described conditions, the average particle diameter of the vinyl polymer particles containing the water-soluble fluorescent dye therein is more reliably 0.01-2. It can be formed to be in the range of 0 μm.

The vinyl polymer particles obtained by this emulsion polymerization may be isolated from the aqueous medium, and may not be isolated if necessary.
Polymer particles are isolated by centrifuging by using a centrifuge to settle and separate the particles, spray drying method represented by spray dryer, and heated rotating drum represented by drum dryer and drying. It can be carried out by a method such as lyophilization.

  The present invention is not intended to limit the production method of vinyl polymer particles and the vinyl polymer particles to those exemplified above, but to the extent that the effects of the present invention are not significantly impaired by conventional technical matters. It can be adopted as appropriate.

  EXAMPLES Next, although an Example is given and this invention is demonstrated in more detail, this invention is not limited to these.

(About average particle size)
The average particle diameter in the following Examples and Comparative Examples means the Z average particle diameter measured using a method called dynamic light scattering unless otherwise specified.
That is, an aqueous dispersion in which vinyl polymer particles are dispersed in water is irradiated with laser light, and the intensity of scattered light scattered from the vinyl polymer particles is measured over time in microseconds. This is the Z average particle diameter obtained by a cumulant analysis method for calculating the average particle diameter by applying the scattering intensity distribution due to the polymer particles to a normal distribution.
This type of average particle diameter can be easily measured with a commercially available measuring apparatus. In this example, “Zeta Sizer Nano ZS” commercially available from Malvern is used for measurement.
The above-mentioned commercially available measuring apparatus is equipped with data analysis software, and the Z average particle diameter can be calculated by automatically analyzing the measurement data.

Example 1
After adding 0.3 g of rhodamine B to 20 g of 2-methacryloyloxyethyl succinic acid (Kyoeisha, Light Ester HOMS), the mixture was stirred for 5 hours using a mechanical stirrer.
The resulting solution dissolved Rhodamine B uniformly, and no dissolution residue was observed.
To this solution, 10 g of glycidyl methacrylate (Kyoeisha, Light Ester GMA) and 70 g of styrene were added as a crosslinking component and stirred to prepare a polymerizable composition.
Next, an aqueous medium in which 0.3 g of sodium styrenesulfonate as a surfactant and 1.0 g of ammonium peroxodisulfate as a polymerization initiator was dissolved in 400 g of ion-exchanged water was added to a 2 L autoclave, and nitrogen substitution was performed. Emulsification was performed by stirring.
After sufficiently purging with nitrogen, the autoclave was sealed, and emulsion polymerization was carried out for 6 hours while maintaining the stirring speed at 300 rpm and the internal temperature at 70 ° C.
Subsequently, the emulsion was cooled to room temperature to complete the polymerization.
After completion of the polymerization, the vinyl polymer particles were settled with a centrifuge (precipitation separation), and after removing the supernatant aqueous solution, ion exchanged water was added and dispersed again. This operation is repeated three times to wash the vinyl polymer particles to remove reaction residues such as a polymerization initiator, and then further disperse in ion exchange water to give a vinyl heavy polymer having a solid content of 10% by weight. An aqueous dispersion of coalesced microparticles was obtained.

The obtained vinyl polymer particles had a Z average particle diameter of 0.454 μm, and no aggregates of vinyl polymer particles were observed.
Further, during centrifugation, the separated aqueous solution was not colored due to the elution of rhodamine B.
Next, 1 g of the above aqueous dispersion of vinyl polymer microparticles was taken in a 100 ml beaker and again irradiated with black light. The dispersion showed a fluorescent red color.
Moreover, a mode that the vinyl polymer particle obtained in this Example 1 was observed with the scanning electron microscope (SEM) is shown in FIG.
The scale in the lower right of FIG. 1 when viewed from the front corresponds to a total length of 10 μm.
As shown in this figure, in Example 1, it can be seen that fine and homogeneous vinyl polymer particles are obtained.

(Example 2)
As shown in Table 1, the amount of rhodamine B added was changed to 0.1 g instead of 0.3 g, acrylic acid was used instead of 2-methacryloyloxyethyl succinic acid, and the amount of sodium styrenesulfonate added was Emulsion polymerization was carried out in the same manner as in Example 1 except that the amount was changed to 0.2 g instead of 0.3 g to obtain an aqueous dispersion of vinyl polymer microparticles having a solid content of 10% by weight and a red color.
Acrylic acid uniformly dissolves rhodamine B in the pre-polymerization stage, and no dissolution residue is seen. The resulting vinyl polymer particles have a Z-average particle diameter of 0.257 μm and are aggregates of polymer particles. Was not seen.
Further, during centrifugation, the separated aqueous solution was not colored due to the elution of rhodamine B.
Further, when 1 g of the above-mentioned vinyl polymer fine particle aqueous dispersion was taken in a 100 ml beaker and again dispersed in 50 g of water and irradiated with black light, the dispersion showed a fluorescent red color.

(Examples 3 to 5)
The materials used for forming the vinyl polymer particles are as shown in Table 1, and vinyl polymer microparticles are prepared in the same manner as in Examples 1 and 2 except that these are used in the mixing ratio shown in Table 1. did.
It should be noted that elution of rhodamine B was not observed when the vinyl polymer microparticles were centrifuged, and color development was observed when an aqueous dispersion was prepared and irradiated with black light. The same as in the first and second embodiments.
The average particle diameter of the obtained vinyl polymer particles is also shown in Table 1.

(Comparative Example 1)
As shown in Table 1, vinyl polymer particles were prepared without using the 2-methacryloyloxyethyl succinic acid used in Example 1.
That is, after adding 0.3 g of rhodamine B to 70 g of styrene and 10 g of glycidyl methacrylate, the mixture was stirred for 5 hours using a mechanical stirrer.
However, rhodamine B was hardly dissolved and remained as a solid.
Therefore, stirring was further performed for 10 hours, but no significant change was found in the dissolved state.
Next, a polymerizable composition containing the above rhodamine B dissolution residue in a 2 L autoclave, and 400 g of ion-exchanged water in which 0.3 g of sodium styrenesulfonate as a surfactant and 1.0 g of ammonium peroxodisulfate as a polymerization initiator were dissolved were added. The mixture was emulsified with a stirrer under nitrogen substitution.
Except for the above, the same procedure as in Example 1 was performed to obtain an aqueous dispersion of vinyl polymer microparticles having a solid content of 10% by weight.
However, the resulting aqueous dispersion of vinyl polymer microparticles was hardly colored red (white).
The vinyl polymer particles thus obtained had a Z average particle diameter of 0.273 μm and no aggregates of vinyl polymer particles were observed. However, 1 ml of the above aqueous dispersion of vinyl polymer microparticles was 100 ml. When the solution taken in a beaker and again dispersed in 50 g of water was irradiated with black light, the solution did not exhibit fluorescence.
Furthermore, the aqueous solution separated during the centrifugation exhibited a deep red color due to the elution of rhodamine B.

(Comparative Example 2)
Emulsion polymerization was carried out in the same manner as in Example 1 except that glycidyl methacrylate as a crosslinking component was not added.
As a result, the temperature inside the autoclave was raised to 70 ° C., and stirring was stopped after about one hour.
Then, when the autoclave was opened after cooling to room temperature, the emulsion was gelled and the entire system was solidified, and vinyl polymer particles could not be obtained.

(Comparative Example 3)
Emulsion polymerization was carried out in the same manner as in Example 1 except that divinylbenzene was used instead of glycidyl methacrylate.
As a result, rhodamine B was uniformly dissolved in the polymerizable composition, and the presence of dissolution residue was not observed. However, when the inside of the autoclave was confirmed after the completion of emulsion polymerization, the mixed solution contained a large number of resin lumps. The slurry was highly viscous.
In addition, after the obtained polymer was washed and the resin mass was removed, it was observed with an optical microscope and a scanning electron microscope (SEM), and a large number of fine vinyl polymer particles were firmly bound to about 10 μm. It became clear that it became the aggregate of the magnitude | size, and it became clear that the target microparticle was not obtained.

  Thus, according to the present invention, fine vinyl polymer particles encapsulating a water-soluble fluorescent dye can be easily formed, and the obtained particles are used as a fluid visualization device tracer and a flow site accuracy control. It can also be seen from the above results that the present invention is suitable for use in microfluidic devices and the like that require extremely fine particle diameters, such as in the field of standard particles for use and carriers for immunodiagnostics.

Claims (5)

A vinyl polymer particle containing a water-soluble fluorescent dye is prepared by dispersing a vinyl monomer and a water-soluble fluorescent dye in an aqueous medium and polymerizing the vinyl monomer. A manufacturing method comprising:
The average particle diameter of the vinyl polymer particles to be produced is any one of 0.01 to 2 μm,
The polymerization is an emulsion polymerization performed in the presence of a surfactant and a polymerization initiator, and as the vinyl monomer, a vinyl monomer having a carboxyl group, and the vinyl monomer The emulsion polymerization is carried out by dispersing a vinyl monomer having a functional group capable of binding to a carboxyl group in the aqueous medium ,
The method for producing vinyl polymer particles, wherein the vinyl monomer in the emulsion polymerization contains the vinyl monomer having a carboxyl group in a proportion of 20% by weight to 40% by weight. . 2. The vinyl monomer according to claim 1, wherein the vinyl monomer in the emulsion polymerization contains a vinyl monomer having a functional group capable of binding to a carboxyl group in a proportion of 10 wt% or more and 20 wt% or less. Production method of polymer particles.   The method for producing vinyl polymer particles according to claim 1 or 2, wherein the functional group capable of binding to the carboxyl group is a glycidyl group.   The method for producing vinyl polymer particles according to any one of claims 1 to 3, wherein the water-soluble fluorescent dye is a rhodamine dye. Vinyl polymer particles containing the water-soluble fluorescent dye by dispersing a vinyl monomer and a water-soluble fluorescent dye in an aqueous medium and polymerizing the vinyl monomer,
The polymerization is an emulsion polymerization performed in the presence of a surfactant and a polymerization initiator, and the emulsion polymerization includes a vinyl monomer having a carboxyl group as the vinyl monomer, and the vinyl The vinyl monomer having a functional group capable of binding to the carboxyl group of the monomer is dispersed in the aqueous medium, and the vinyl monomer having a carboxyl group is contained in the vinyl monomer. characterized in that the average particle size by Rukoto the emulsion polymerization is contained is carried out mer in an amount of 20% by weight to 40% by weight is formed to be one of the 0.01~2μm Vinyl polymer particles.