JP2014160051A - Core shell type particle for column, and manufacturing method for the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a core shell type particle for a column in which resistance to pressure, theoretical plate number and degree of peak symmetry are improved, and a manufacturing method for the same.SOLUTION: A core shell type particle for a column includes a parent particle and a plurality of child particles adhered on an outside of the parent particle. A manufacturing method of the core shell type particle for a column having the parent particle and the plurality of child particles adhered on the outside of the parent particle, includes the steps of: adsorbing polyelectrolyte to the outside of the parent particle which has a functional group, and adsorbing the child particles to the outside of the polyelectrolyte.

Description

  The present invention relates to a core-shell type particle suitable as a packing material for separation, fractionation, analysis, and purification columns, and a method for producing the same.

  Porous silica or a porous polymer that is organic particles is used as a packing material for separation, fractionation, and analysis. Where necessary, functional groups have been formed on the outside of porous silica and porous polymers to separate, sort, and analyze specific substances. Organic particles are advantageous in that various characteristics can be obtained depending on the type of monomer used for synthesis (styrene, divinylbenzene, acrylic resin, agarose, etc.) (see, for example, Patent Documents 1 to 3). Most of the organic particles are used for these. Disadvantages include the fact that the flow rate during separation, fractionation, and analysis is limited because it is easily deformed by pressure. Although the pressure resistance can be controlled by increasing the degree of crosslinking of the resin, the original advantages of organic matter are lost because the monomers used are limited. Furthermore, particle swelling and shrinkage occur depending on the type of mobile phase.

  On the other hand, porous silica has relatively good pressure resistance, and can improve separation performance by reducing the diameter. In the analysis, a column using particles in which organic functional groups (octadecyl (carbon number 18), octyl (carbon number 8), phenyl, etc.) are adsorbed on the outside of the porous silica is used. However, in high performance liquid chromatography applications, pressure resistance is further required by further reducing the diameter. Patent Document 4 describes a core-shell type silica with improved pressure resistance. In this case, the core shell is a core shell meaning that the central portion is made nonporous, and the pressure reduction effect is insufficient.

  The smaller the particle diameter of the column particles, the more the theoretical plate number is improved. However, since the pressure reduction and the theoretical plate number increase are in a trade-off relationship, the smaller the particle diameter of the column particles, the higher the pressure in the column, which makes it difficult to use the column.

  Furthermore, with the recent development of polymerization techniques such as seed polymerization and classification techniques, attempts have been made to use monodisperse particles in columns (see, for example, Patent Documents 5 and 6). However, if the monodispersity of the particles is increased, the particles are easily arranged, and column packing at a predetermined pressure becomes difficult. A column packed with such particles causes various problems such as pressure increase, theoretical plate number decrease, peak symmetry decrease, and peak tailing. In addition, there is a method of improving the number of theoretical plates by appropriately mixing two types of monodisperse particles, but such a method is complicated.

Japanese Patent Laid-Open No. 11-171947 Japanese Patent No. 4335168 Special table 2003-509549 gazette International Publication No. 2007/122930 Japanese Patent No. 3628493 Special table 2003-509549 gazette

  An object of the present invention is to provide a core-shell type particle for a column and a method for producing the same, in which the above problems are improved and the column pressure, the number of theoretical plates and the peak symmetry are improved.

  The present invention relates to a core-shell type particle for a column comprising a parent particle and a plurality of child particles attached to the outside of the parent particle. Such a core-shell type particle for a column is suitable as a packing material for separation, fractionation, analysis, and purification.

  The present invention also relates to the above-described core-shell type particle for a column, in which the child particles are attached to the outside of the parent particles by chemical bonding.

  The present invention also relates to the above-described core-shell type particle for a column, in which the child particles are attached to the outside of the parent particle through a chemical bond via a polymer.

  The present invention also relates to the above-described core-shell type particle for a column, wherein the coverage of the child particles is in the range of 10 to 70% with respect to the total surface area of the parent particles.

  The present invention also relates to the above-described core-shell particle for a column, wherein the child particles are semicircular particles.

  The present invention also relates to the above-described core-shell type particle for a column, wherein the child particles are spherical particles having irregularities on the surface.

  Further, the present invention is a method for producing a core-shell type particle for a column comprising a parent particle and a plurality of child particles attached to the outside of the parent particle, wherein the polymer electrolyte is provided outside the parent particle having a functional group. The present invention relates to a method for producing core-shell type particles for a column, comprising a step of adsorbing particles and a step of adsorbing child particles on the outside of the polymer electrolyte.

  Moreover, this invention relates to the manufacturing method of said core-shell type particle | grains for columns whose said functional group is a carboxyl group.

  The present invention also relates to a method for producing the above-described core-shell type particle for a column, wherein the polymer electrolyte is a polyamine.

  The present invention also relates to a method for producing the above-described core-shell type particle for a column, wherein the polymer electrolyte is polyethyleneimine.

  ADVANTAGE OF THE INVENTION According to this invention, the core shell type particle | grain for columns which reduced the pressure rise, improved the theoretical plate number, and improved the symmetry of the peak can be provided.

  Hereinafter, embodiments of the present invention will be described in detail.

  In this embodiment, a core-shell type particle for a column (hereinafter, also referred to as “core-shell particle”) is obtained by chemically bonding and immobilizing a child particle on the outside of the parent particle.

  The average particle size of the parent particles is preferably 0.2 to 100 μm for the purpose of improving the number of theoretical plates for analytical use, and preferably 30 to 300 μm for preparative / separation use.

  In addition, the average particle diameter here is obtained by imaging a plurality of particles with a scanning electron microscope (SEM; for example, product name: S-4800, manufactured by Hitachi High-Technologies Corporation), and measuring the particle diameter by image analysis. The number average particle diameter determined by the method of calculating the average value.

  The particle size distribution of the parent particles is preferably small. The coefficient of variation (C.V.) of the particle diameter is preferably 0.2 or less, more preferably 0.15 or less, still more preferably 0.1 or less, and particularly preferably 0.05 or less. The smaller the coefficient of variation, the higher the number of theoretical plates. Theoretically, a smaller coefficient of variation is better. However, if the dispersion becomes too monodisperse, particles are aligned, making it difficult to fill the column. In such a case, there is a method of improving the number of theoretical plates by appropriately mixing two types of monodisperse particles, but it is cumbersome, and using the core-shell particles as in this embodiment, the core-shell type particles can be packed into the column. Simple and preferable.

  The parent particle may be an inorganic particle such as silica or an organic particle, but the organic particle is likely to have the effect of the present invention (because pressure resistance is originally low). Hereinafter, the organic particles will be described in detail, but even inorganic particles are effective.

  The sphericity of the parent particle is preferably 0.8 or more, more preferably 0.9 or more, and still more preferably 0.95 or more. The sphericity is observed with a scanning electron microscope (SEM), 1000 particles are photographed, the major axis and minor axis are measured by image analysis, and the individual sphericity (minor axis / major axis) is calculated and averaged. Can be obtained as

  Examples of the method for synthesizing the parent particles include seed polymerization and suspension polymerization, and seed polymerization is preferable because it can easily synthesize relatively monodisperse particles.

  Seed polymerization is a synthesis method in which seed particles having a size of several hundred nm to several tens of μm are swollen to be several times larger, and polymerization is performed. The seed particles are generally synthesized by soap-free emulsion polymerization or precipitation polymerization, but are preferably synthesized by soap-free emulsion polymerization from the viewpoint of easy synthesis of monodisperse particles.

  The soap-free emulsion polymerization is carried out in water, alcohol or a water / alcohol mixed solvent, and water is preferred from the viewpoint of cost. Specifically, a reaction initiator and a monomer are put in a solvent, and the polymer is grafted on the surface by radical polymerization. Any monomer having a vinyl group can be used. Monomers include monovinyl aromatic monomers, acrylic monomers, vinyl ester monomers, vinyl ether monomers, monoolefin monomers, halogenated olefin monomers, diolefin monomers, etc. Is mentioned.

  Specifically, styrene, o-methylstyrene, m-methylstyrene, p-methylstyrene, p-ethylstyrene, 2,4-dimethylstyrene, pn-butylstyrene, p-tert-butylstyrene, p- n-hexyl styrene, pn-octyl styrene, pn-nonyl styrene, pn-decyl styrene, pn-dodecyl styrene, p-methoxy styrene, p-phenyl styrene, p-chloro styrene, 3, Styrene such as 4-dichlorostyrene and derivatives thereof, ethylene unsaturated monoolefins such as ethylene, propylene, butylene and isobutylene, vinyl halides such as vinyl chloride, vinylidene chloride, vinyl bromide and vinyl fluoride, vinyl acetate , Vinyl esters such as vinyl propionate, vinyl benzoate and vinyl butyrate, Methyl acrylate, ethyl acrylate n-butyl acrylate, isobutyl acrylate, propyl acrylate, n-octyl acrylate, dodecyl acrylate, 2-ethylhexyl acrylate, stearyl acrylate, 2-chloroethyl acrylate, phenyl acrylate, α-chloromethyl acrylate, methyl methacrylate, ethyl methacrylate, propyl methacrylate, n-butyl methacrylate, isobutyl methacrylate, n-octyl methacrylate, dodecyl methacrylate, 2-ethylhexyl methacrylate, stearyl methacrylate, methacryl Α-methylene aliphatic monocarboxylic acid such as phenyl acid, dimethylaminoethyl acrylate, dimethylaminoethyl methacrylate, diethylaminoethyl acrylate, diethylaminoethyl methacrylate, etc. Acrylic acid or methacrylic acid derivatives such as tellurium, acrylonitrile, methacrylonitrile, acrylamide, methacrylamide, 2-hydroxyethyl acrylate, 2-hydroxypropyl acrylate, 2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, etc. Can be used as a monomer, and in some cases, acrylic acid, methacrylic acid, maleic acid, fumaric acid and the like can also be used. Further, 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 mentioned as monomers. Among these, it is preferable to use styrene or methyl methacrylate from the viewpoint of ease of polymerization.

  Any polymerization initiator may be used as long as it is used in ordinary emulsion polymerization. For example, persulfates such as potassium persulfate, sodium persulfate and ammonium persulfate, and organic peroxides such as benzoyl hydroperoxide. And azo compounds such as azobisisobutyronitrile. It can also be used as a redox initiator in combination with a reducing agent as required.

  Here, if the molecular weight of the polymer used as the seed particles is too large, it is difficult to swell during seed polymerization. For this reason, the weight average molecular weight of the polymer used as the physically adsorbed seed particles is preferably 100,000 or less.

  The weight average molecular weight of the polymer can be determined by conversion from a calibration curve using standard polystyrene by gel permeation chromatography (GPC). The calibration curve can be obtained by approximating with a cubic equation using a standard polystyrene 5-sample set (PStQuick MP-H, PStQuick B (trade name, manufactured by Tosoh Corporation)).

The GPC conditions are shown below.
(GPC conditions)
Apparatus: (Pump: L-2130 type (manufactured by Hitachi High-Technologies Corporation)),
(Detector: L-2490 type RI (manufactured by Hitachi High-Technologies Corporation)),
(Column oven: L-2350 (manufactured by Hitachi High-Technologies Corporation))
Column: Gelpack GL-R440 + Gelpack GL-R450
+ Gelpack GL-R400M (3 in total) (trade name, manufactured by Hitachi Chemical Co., Ltd.)
Column size: 10.7 mmI. D x 300mm
Eluent: Tetrahydrofuran Sample concentration: 10 mg / 2 mL
Injection volume: 200 μL
Flow rate: 2.05 mL / min Measurement temperature: 25 ° C

  In the soap-free emulsion polymerization, a method in which oxygen is dissolved as required and a method in which a chain transfer agent is added are preferable. As the chain transfer agent, monosulfide or disulfide chain transfer agents are preferable.

  Next, seed particles are dispersed in one of water, alcohol, and water / alcohol mixed solvent, and seed polymerization is performed. In general, seed polymerization is generally performed by methods shown in Colloid & Polymer Science, 267, 193-200 (1989) and Colloid & Polymer Science, 274, 279-284 (1996). That is, in the presence of seed particles synthesized with an uncrosslinked resin, polymerization is performed using the medium-soluble polymerization initiator in a medium that dissolves the polymerizable vinyl monomer but does not dissolve the resulting polymer. Do.

  Specifically, the following method is used. First, a seed particle dispersion medium is prepared. Next, a polymerization initiator, a polymerizable vinyl monomer, a surfactant, a porous agent and the like are added as appropriate, and emulsified with a homogenizer or the like. The emulsified liquid is added to the dispersion medium, and the seed particles are swollen over several hours to several tens of hours. The swelling speed varies depending on the molecular weight of the polymer used as seed particles and the type of polymerizable vinyl monomer.

  As the polymerizable vinyl monomer, a polyvinyl monomer, a mixture of a polyvinyl monomer and a monovinyl monomer, or the like can be used.

  As the polyvinyl monomer, an aromatic polyvinyl monomer or a fatty aromatic polyvinyl monomer is preferable. Examples of the aromatic polyvinyl monomer include bisvinylphenylalkanes such as divinylbenzene, bisphenylmethane, and bisvinylphenylethane, and examples of the aliphatic polyvinyl monomer include poly (meth) acrylates or alkylenepoly ( Meth) acrylamide is preferred. Specific examples include (poly) ethylene glycol di (meth) acrylate, glycerin di (meth) acrylate, trimethylolpropane tri (meth) acrylate, and tetrahydroxybutane di (meth) acrylate.

  The proportion of the polyvinyl monomer is preferably 1 to 100% by mass and more preferably 20 to 100% by mass based on the total mass of the polymerizable vinyl monomer from the viewpoint of pressure resistance. If it is out of this range, the obtained polymer is easily dissolved, the pressure resistance is not sufficient, and it tends to be easily broken.

  As the monovinyl monomer, the above-mentioned monovinyl aromatic monomer, acrylic monomer, vinyl ester monomer, vinyl ether monomer, monoolefin monomer, halogenated olefin monomer, etc. Can be used.

  Examples of the porous agent include aliphatic or aromatic hydrocarbons, esters, ketones, ethers, and alcohols, which are organic solvents that act as a phase separation agent during seed polymerization and promote particle porosity. Can be mentioned. Specific examples include toluene, xylene, cyclohexane, octane, butyl acetate, dibutyl phthalate, methyl ethyl ketone, diethylbenzene, dibutyl ether, 1-hexanol, 2-octanol, decanol, lauryl alcohol, cyclohexanol and the like. Or it can mix and use.

  The porous agent can be used in an amount of 0 to 200% by mass with respect to the polymerizable vinyl monomer. The porosity of the particles can be controlled by the amount of the porous agent. Further, the size and shape of the pores can be controlled by the kind of the porous agent.

  Any polymerization initiator may be used as long as it is used in ordinary emulsion polymerization. Examples thereof include persulfates such as potassium persulfate, sodium persulfate, and ammonium persulfate, and organic compounds such as benzoyl peroxide and benzoyl hydroperoxide. Peroxides, azo compounds such as azobisisobutyronitrile, and the like. It can also be used as a redox initiator in combination with a reducing agent as required.

  After swelling, the reaction is carried out for several hours to several tens of hours at a temperature suitable for the reaction temperature of the initiator. Nitrogen can be substituted before the reaction. The reaction temperature is usually in the range of 40 ° C to 90 ° C. If the dispersibility of the particles is controlled with polyvinyl alcohol or the like before the reaction, the aggregation of the particles can be alleviated.

  The particle size is determined by the total amount of the polymerization initiator, the polymerizable vinyl monomer, and the porous agent. With seed polymerization, particles having an average particle diameter of 1 to 100 μm can be synthesized.

  The child particles are coated on the outside of the parent particles synthesized as described above. The average particle diameter of the child particles is preferably 0.1 to 20% of the average particle diameter of the parent particles. If it is less than 0.1%, the pressure resistance improving effect is insufficient, and if it exceeds 20%, coating tends to be difficult. The average particle diameter of the child particles is preferably in the range of 10 nm to 20 μm.

  The composition of the child particles may be a resin system or an inorganic system. In the case of a resin system, it is preferable that the composition is as close as possible to that of the parent particle, and examples thereof include a styrene / divinylbenzene copolymer resin. In the case of an inorganic system, for example, silica and the like can be mentioned.

  The child particles are preferably semicircular particles or spherical particles (potato-like particles) having irregularities on the surface. When such a child particle is used, the binding force between the parent particle and the child particle becomes strong.

  In the present specification, the “semicircular particle” is defined as a particle that has a circular portion in two dimensions and is not spherical. The semicircular particles are preferably flat and red blood cells. In the present specification, the erythrocyte-shaped particles may have dents on both sides, or may have dents only on one side (hereinafter also referred to as bowl-shaped particles).

  Such polymer particles are preferably synthesized by emulsion polymerization, more preferably by soap-free emulsion polymerization. In emulsion polymerization, a surfactant such as sodium alkylbenzene sulfonate or sodium alkyl sulfate may be used, but using soap-free emulsion polymerization is simple and does not require subsequent washing, so particles can be produced at low cost. Can be synthesized.

  As the monomer used for the soap-free emulsion polymerization, any monomer having a vinyl group can be used. Examples thereof include a monovinyl aromatic monomer, an acrylic monomer, a vinyl ester monomer, a vinyl ether monomer, a monoolefin monomer, a halogenated olefin monomer, and a diolefin monomer.

  Specifically, styrene, o-methylstyrene, m-methylstyrene, p-methylstyrene, p-ethylstyrene, 2,4-dimethylstyrene, pn-butylstyrene, p-tert-butylstyrene, p- n-hexyl styrene, pn-octyl styrene, pn-nonyl styrene, pn-decyl styrene, pn-dodecyl styrene, p-methoxy styrene, p-phenyl styrene, p-chloro styrene, 3, Styrene such as 4-dichlorostyrene and derivatives thereof, ethylene unsaturated monoolefins such as ethylene, propylene, butylene and isobutylene, vinyl halides such as vinyl chloride, vinylidene chloride, vinyl bromide and vinyl fluoride, vinyl acetate , Vinyl esters such as vinyl propionate, vinyl benzoate and vinyl butyrate, Methyl acrylate, ethyl acrylate n-butyl acrylate, isobutyl acrylate, propyl acrylate, n-octyl acrylate, dodecyl acrylate, 2-ethylhexyl acrylate, stearyl acrylate, 2-chloroethyl acrylate, phenyl acrylate, α-chloromethyl acrylate, methyl methacrylate, ethyl methacrylate, propyl methacrylate, n-butyl methacrylate, isobutyl methacrylate, n-octyl methacrylate, dodecyl methacrylate, 2-ethylhexyl methacrylate, stearyl methacrylate, methacryl Α-methylene aliphatic monocarboxylic acid such as phenyl acid, dimethylaminoethyl acrylate, dimethylaminoethyl methacrylate, diethylaminoethyl acrylate, diethylaminoethyl methacrylate, etc. Acrylic acid or methacrylic acid derivatives such as tellurium, acrylonitrile, methacrylonitrile, acrylamide, methacrylamide, 2-hydroxyethyl acrylate, 2-hydroxypropyl acrylate, 2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, etc. Can be used as a monomer, and in some cases, acrylic acid, methacrylic acid, maleic acid, fumaric acid and the like can also be used. Further, 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 mentioned as monomers.

  Among these, styrene and its derivatives, acrylic acid esters and derivatives thereof, and vinyl esters are preferable, and styrene and its derivatives are more preferable from the viewpoint of ease of polymerization and easy shape of semicircular particles. Moreover, you may use the said monomer in combination of 2 or more types.

  In this embodiment, in order to obtain the shape of a semicircular particle, a method of mixing an alkoxysilane having a polymerizable double bond, that is, an alkoxysilane having a C═C double bond can be mentioned. From the viewpoint of influencing the particle shape, it is preferable to mix an alkoxysilane having a C═C double bond of 0.3 mol% or more with respect to all monomers. Examples of the alkoxysilane having a C = C double bond include 3-methacryloxypropylmethyldimethoxysilane, 3-methacryloxypropyltrimethoxysilane, 3-methacryloxypropylmethyldiethoxysilane, and 3-methacryloxypropyltriethoxysilane. , 3-acryloxypropyltrimethoxysilane and the like. By mixing alkoxysilane, the solvent resistance can be improved.

  In order to impart weather resistance, moisture resistance, solvent resistance, breaking strength, and insulation to the child particles, it is preferable to add a crosslinkable monomer having a plurality of polymerizable vinyl groups. Examples of such crosslinkable monomers include aromatic divinyls such as divinylbenzene and divinylnaphthalene, ethylene glycol di (meth) acrylate, diethylene glycol di (meth) acrylate, and triethylene glycol tri (meth) acrylate.

  When there are too many crosslinkable monomers, even if it contains the alkoxysilane which has a double bond which has a superposition | polymerization property of 0.3 mol% or more with respect to all the monomers, a child particle will not become semicircular easily.

  The ratio of the alkoxysilane having a double bond and the crosslinkable monomer (alkoxysilane having a double bond / crosslinkable monomer) is preferably 0.2 or more. When the ratio is less than 0.2, the obtained child particles tend to be nearly spherical.

  Any polymerization initiator may be used as long as it is used in ordinary emulsion polymerization. For example, persulfates such as potassium persulfate, sodium persulfate and ammonium persulfate, and organic peroxides such as benzoyl hydroperoxide. And azo compounds such as azobisisobutyronitrile. It can also be used as a redox initiator in combination with a reducing agent as required. In order to produce a child particle emulsion, polymerization is usually carried out by dropping various monomers all at once, in a divided manner or continuously in the presence of the surfactant or polymerization initiator. When performing soap-free emulsion polymerization, by incorporating a hydrophilic reactive monomer, particles can be stably synthesized, and particle diameter control is facilitated. Specific examples include sodium styrene sulfonate, methacrylic acid, and sodium methacrylate. If a large amount of hydrophilic reactive monomer is added, the particle size becomes small, and if a small amount of hydrophilic reactive monomer is added, the particle size becomes large.

These monomers are added all at once, divided or continuously, and stirred under a nitrogen atmosphere to carry out emulsion polymerization. As the solvent, pure water from which ions have been removed is used. The polymerization temperature is preferably 40 ° C. to 90 ° C., and the reaction time is preferably 2 hours to 10 hours. The stirring speed is preferably from 100 to 500 min- ¹ .

  The shape of the semicircular particles to be synthesized can be adjusted by the amount of the crosslinkable monomer or the alkoxysilane having a double bond.

  The larger the ratio of alkoxysilane having a double bond to the crosslinkable monomer (alkoxysilane having a double bond / crosslinkable monomer), the ratio of the thickness (d) to the flat surface diameter (D). (D / D) decreases, and the larger the amount of alkoxysilane having a double bond, the smaller (d / D). The d / D ratio is preferably in the range of 0.1 to 1.0, and more preferably in the range of 0.2 to 0.8. When the ratio of d / D is less than 0.2, it becomes difficult to coat the child particles on the parent particles, and when it is more than 0.8, the risk of child particle dropping increases although it can be used.

  The particle size variation of the child particles is C.I. V. <10% is preferred, C.I. V. More preferably, it is <3%. In this case, the particle diameter is expressed by a volume average particle diameter, and can be measured with a Coulter counter or the like.

  The child particles may also be spherical particles having irregularities on the surface. When an alkoxysilane having a double bond and a crosslinkable monomer are added in the same molar amount, such a shape may be obtained.

  After the parent particles and the child particles are synthesized separately by the method as described above, the child particles are chemically coated on the outside of the parent particles.

  As a method for bonding the parent particle and the child particle, a method of heteroaggregating the parent particle having a functional group and the child particle having a functional group may be mentioned. In this case, there is a method of reacting in the presence of a catalyst with a combination of an amino group and a carboxyl group, a glycidyl group and an amino group, a hydroxyl group and a hydroxyl group, or the like.

  Furthermore, when it is going to reinforce bondability, the method of making it couple | bond through a polymer | macromolecule is mentioned.

  In this case, a carboxyl group, an isocyanate group, and a glycidyl group are introduced into the parent particle in advance on the particle surface, while a carboxyl group, an isocyanate group, and a glycidyl group are also introduced into the child particle on the particle surface. A conventionally known method can be used for these. Among them, a carboxyl group that can be easily introduced is preferable. Specifically, in the case of resin particles, for example, a small amount (about 1% by mass) of acrylic acid, acrylate, or the like is added when synthesizing parent particles or child particles. , Parent particles or child particles coated with carboxyl groups can be obtained. In the case of inorganic particles such as silica, inorganic particles having a carboxyl group can be synthesized by treatment with a silane coupling agent having a carboxyl group.

  Next, the child particles are coated on the surface of the parent particles having functional groups. The surface potential (zeta potential) of the parent particles and the child particles having a carboxyl group, an isocyanate group, or a glycidyl group is usually (the pH is in a neutral region). B) is negative. It is difficult to coat particles having a negative surface potential around particles having a negative surface potential.

Therefore, a method of alternately laminating the polymer electrolyte and the child particles is preferable. As a more specific manufacturing method,
(1) Dispersing the parent particles having a functional group in a polymer electrolyte solution, adsorbing the polymer electrolyte on the surface of the parent particles, and then rinsing;
(2) The parent particles are dispersed in the dispersion solution of the child particles, the child particles are adsorbed on the surface of the parent particles, and then rinsed, whereby the polymer electrolyte and the child particles are laminated on the surface. Particles can be produced.

  Such a method is called an alternating lamination method (Layer-by-Layer assembly). The alternate lamination method is described in G.H. This is a method for forming an organic thin film published in 1992 by Decher et al. (Thin Solid Films, 210/211, p. 831 (1992)). In this method, a polycation adsorbed on a substrate by electrostatic attraction by alternately immersing the base material in an aqueous solution of a polymer electrolyte having a positive charge (polycation) and a polymer electrolyte having a negative charge (polyanion). A combination of polyanions is laminated to obtain a composite film (alternate laminated film).

  In the alternating layering method, the film is grown by attracting the charge of the material formed on the substrate and the material having the opposite charge in the solution by electrostatic attraction, so that the adsorption proceeds and the charge is neutralized. When this occurs, no further adsorption occurs. Therefore, when reaching a certain saturation point, the film thickness does not increase any more.

  Lvov et al. Reported on a method in which the alternating lamination method is applied to fine particles, and a polymer electrolyte having a charge opposite to the surface charge of the fine particles is laminated by an alternating lamination method using fine particle dispersions of silica, titania, and ceria. (Langmuir, Vol. 13, (1997), p. 6195-6203). By using this method, insulating particles having a negative surface charge and polydiallyldimethylammonium chloride (PDDA) or polyethylenimine (PEI), which are polycations having the opposite charge, are alternately laminated to provide insulation. It is possible to form a fine-particle laminated thin film in which neutron particles and polymer electrolyte are alternately laminated.

  After immersing in the dispersion of polymer electrolyte solution or inorganic oxide fine particles, before immersing in the fine particle dispersion or polymer electrolyte solution having the opposite charge, the excess polymer electrolyte solution or inorganic oxide fine particles are rinsed only with a solvent. It is preferred to wash away the dispersion. Examples of such rinsing include water, alcohol, and acetone.

  The polymer electrolyte solution used in this embodiment is dissolved in water or a mixed solvent of an organic solvent. Examples of water-soluble organic solvents that can be used include methanol, ethanol, propanol, acetone, dimethylformamide, acetonitrile, and the like.

  As the polymer electrolyte, a polymer that is ionized in an aqueous solution and has a charged functional group in the main chain or side chain can be used. In this case, it is preferable to use a polycation. The polycation generally has a positively charged functional group such as polyamines, such as polyethyleneimine (PEI), polyallylamine hydrochloride (PAH), polydiallyldimethylammonium chloride ( PDDA), polyvinyl pyridine (PVP), polylysine, polyacrylamide, and a copolymer containing at least one of them can be used.

  Among polyelectrolytes, polyethyleneimine has a high charge density and a strong binding force. Among these polymer electrolytes, alkali metal (Li, Na, K, Rb, Cs) ions, alkaline earth metal (Ca, Sr, Ba, Ra) ions, halides are used in order to avoid ion elution. Those not containing ions (fluorine ions, chloride ions, bromine ions, iodine ions) are preferred.

  These polymer electrolytes are either water-soluble or soluble in organic solvents such as alcohol, and the molecular weight of the polymer electrolyte cannot be generally determined depending on the type of polymer electrolyte used. Those having a weight average molecular weight of about 1,000 to 200,000 are preferred. When the weight average molecular weight is 1,000 or less, the dispersibility of the parent particles is insufficient, and when the particle diameter of the parent particles is 3.0 μm or less, aggregation becomes obvious. In general, the concentration of the polymer electrolyte in the solution is preferably about 0.01 to 10% by mass. Further, the pH of the polymer electrolyte solution is not particularly limited.

  By using the above polymer electrolyte thin film, the surface of the parent particle can be uniformly coated with the child particles without any defects.

  Further, the coverage of the child particles can be controlled by adjusting the type, molecular weight, and concentration of the polymer electrolyte thin film.

  Specifically, when a polymer electrolyte thin film with a high charge density such as polyethyleneimine is used, the coverage of the child particles tends to be high, and a polymer electrolyte thin film with a low charge density such as polydiallyldimethylammonium chloride is used. When used, the coverage of the child particles tends to be low. Further, when the molecular weight of the polymer electrolyte is large, the coverage of the child particles tends to be high, and when the molecular weight of the polymer electrolyte is small, the coverage of the child particles tends to be low. Furthermore, when the polymer electrolyte is used at a high concentration, the coverage of the child particles tends to be high, and when the polymer electrolyte is used at a low concentration, the coverage of the child particles tends to be low.

  The child particles also preferably have a polymer (oligomer) having a weight average molecular weight of 500 to 10,000, more preferably a weight average molecular weight of 1,000 to 4,000, on the surface.

  In this way, by bonding the fine particles having a chemically reactive polymer to each other, it is possible to obtain a strong bond that has not been obtained in the past, and to cope with a decrease in the size of the parent particles and an increase in the size of the child particles.

  It is preferable that the child particles are covered only by one layer because the child particles easily fall off when the layers are laminated.

  The coverage of the child particles is preferably in the range of 10 to 70%, more preferably in the range of 20 to 60%, and still more preferably in the range of 20 to 40%. The coverage here is represented by (surface area of insulating coating portion / total surface area) × 100% by SEM image analysis. Further, the coating variation (CV) is preferably in the range of 0.3 or less. When the coverage of the child particles is in the range of 20 to 60%, the pressure reduction effect is large.

  By heating and drying the core-shell type particles obtained as described above, the bond between the child particles and the parent particles can be strengthened. The reason why the bonding force increases is the chemical bonding between functional groups. The temperature for heating and drying is preferably 60 ° C. to 100 ° C., and the heating time is preferably in the range of 10 to 180 minutes. When the temperature is lower than 60 ° C. or when the heating time is shorter than 10 minutes, the child particles tend to peel off, and when the temperature is higher than 100 ° C. or when the heating time is longer than 180 minutes, the particles tend to be deformed.

  In the present embodiment, it is desirable that at least the parent particle is a porous particle.

The porous particles refer to particles having a surface area of about 50 m ² / g or more. In view of practicality, it is preferably about 80 m ² / g or more, and more preferably 300 m ² / g or more. Small surface areas can adversely affect analysis and separation.

  With respect to the average pore diameter, it is preferable to have an average pore diameter of 30 to 1000 cm. If it is smaller than this, there is a tendency that the number of substances that cannot enter the pores increases, and if it is larger than this, the surface area becomes smaller. These can be adjusted by a pore adjusting agent such as divinylbenzene or toluene. In addition, a pore is a void | hole which exists in a particle | grain surface and an inside, for example, can be formed by removing the above-mentioned pore regulator after a synthesis | combination. It is. The average pore diameter can be measured by a gas adsorption method, a mercury intrusion method, or the like.

  The core-shell type particle for a column produced as described above can be used as a filler for separation, fractionation, analysis, and purification after appropriately adding a functional group such as a sulfonic acid group. In particular, it can be used as a filler for liquid chromatography.

[Example]
EXAMPLES Hereinafter, although an Example demonstrates this invention, this invention is not limited to these Examples.

(Synthesis of seed particles 1 for parent particles)
A 500 mL three-necked flask is charged with 40 g of styrene (ST), 4 g of octanethiol (OCT), 1.98 g of potassium peroxodisulfate (KPS), and 400 g of water, and heated with a water bath at 70 ° C. while stirring. The resulting mixture was stirred for about 8 hours to form seed particles. The seed particles have an average particle size of 0.75 μm and a particle size of C.I. V. = 2.3% and the weight average molecular weight Mw was about 25200. In addition, the particle diameter measurement took a photograph in SEM (Hitachi High-Technologies Corporation make, product name: S-4800), and performed image analysis. Average particle size and C.I. V. Was measured with 2000 particles. The same applies hereinafter.

(Synthesis of porous parent particle 1)
1 g of benzoyl peroxide as a polymerization initiator, 10 g of styrene as a monomer, 2.5 g of divinylbenzene, 3.75 g of toluene as a porous agent, 3.75 g of diethylbenzene, and 0.2 g of methacrylic acid as a carboxyl group introducing agent 92.2% by mass of exchange water, 7.5% by mass of ethanol, and 0.3% of Emar TD (triethanolamine lauryl sulfate, manufactured by Kao Corporation, trade name (“Emar” is a registered trademark)) as a surfactant % Pure water) was dispersed in 340 g, and the mixture was ultrasonically irradiated with a homogenizer for 10 minutes for emulsification. Then, after adding 0.70g of seed particles 1 in solid content, swelling was performed for 20 hours. Thereafter, the temperature was raised to 80 ° C., and polymerization was carried out for 8 hours. After completion of the polymerization, the obtained particles were washed with water and methanol. The synthesized particles have an average particle size of 4.05 μm and a particle size of C.I. V. = 3.3%.

(Synthesis of porous parent particle 2)
The porous particle 2 was synthesized in the same manner as the porous parent particle 1 except that 0.2 g of methacrylic acid was not added.

(Synthesis of child particles 1 to 6)
In 400 g of pure water, materials were added according to the formulation table of child particles 1 to 6 in Table 1, and the mixture was heated at 80 ° C. for 6 hours while stirring at a stirring speed of 200 min ⁻¹ . The synthesized particles were photographed with SEM (S-4800), and image analysis was performed. The average particle size measurement was performed with 100 particles. The same applies hereinafter. The shape of the child particles was either red blood cell shape, potato shape (the surface was bumpy) or spherical.

(Synthesis of core-shell type particle 1 for column)
Next, a 30% by mass polyethyleneimine aqueous solution (manufactured by Wako Pure Chemical Industries, Ltd.) having a weight average molecular weight of 70,000 was diluted with ultrapure water to obtain a 0.3% by mass polyethyleneimine aqueous solution. 10 g of the porous particles 1 having a carboxyl group were added to the 0.3 mass% polyethyleneimine aqueous solution, and the mixture was stirred at room temperature for 15 minutes. Next, the porous particles were filtered with a membrane filter (manufactured by Millipore) having a pore size of 3 μm, put in 200 g of ultrapure water, and stirred at room temperature for 5 minutes. Further, the porous particles are filtered through a membrane filter (Millipore) having a pore diameter of 3 μm, washed with 200 g of ultrapure water twice on the membrane filter to remove the unadsorbed polyethyleneimine, Porous particles having an amino group-containing polymer were prepared.

  Next, a methanol dispersion medium (solid content: 10% by mass) of child particles 1 having a carboxyl group on the surface was prepared.

  Next, the porous particles treated with the polyethyleneimine are immersed in isopropyl alcohol, and a methanol dispersion medium of the child particles 1 having a carboxyl group is dropped on the surface thereof, so that the child particle coverage is 40%. Particles were made. The coverage was adjusted by the dropping amount.

  Thereafter, it was treated with concentrated sulfuric acid to introduce sulfonic acid groups on the surface. Specifically, 57 g of dichloroethane and 92 g of 97% by mass sulfuric acid were added to 10 g of the porous particles, and reacted at 110 ° C. for 4 hours to synthesize core-shell type porous polymer particles into which sulfonic acid groups were introduced.

  Then, the core-shell type particle | grains 1 for columns were produced by heat-drying on conditions of 80 degreeC and 1 hour.

(Synthesis of core-shell type particle 2 for column)
Column core-shell type particles 2 were prepared in the same manner as the column core-shell type particle 1 except that the child particles 2 were used instead of the child particles 1.

(Synthesis of core-shell type particle 3 for column)
Column core-shell type particles 3 were prepared in the same manner as the column core-shell type particles 1 except that the child particles 3 were used instead of the child particles 1.

(Synthesis of core-shell type particle 4 for column)
The core-shell type particle 4 for columns was produced by the same method as the core-shell type particle 1 for columns except having used the child particle 4 instead of the child particle 1.

(Synthesis of column core-shell particles 5)
Column core-shell particles 5 were prepared in the same manner as the column core-shell particles 1 except that the child particles 5 were used instead of the child particles 1.

(Synthesis of core-shell type particles 6 for columns)
Column core-shell particles 6 were produced in the same manner as the column core-shell particles 1 except that the child particles 6 were used instead of the child particles 1.

(Synthesis of core-shell type particle 7 for column)
Column core-shell particles 7 were prepared in the same manner as the column core-shell particles 1 except that the child particle coverage was 10%.

(Synthesis of core-shell particle 8 for column)
Column core-shell particles 8 were produced in the same manner as the column core-shell particles 1 except that the child particle coverage was 60%.

(Synthesis of core-shell particle 9 for column)
A column core-shell type particle 9 was prepared in the same manner as the column core-shell type particle 1 except that the porous parent particle 2 was used instead of the porous parent particle 1.

(Normal particles)
To 10 g of the porous parent particle 1, 57 g of dichloroethane and 92 g of 97% by mass sulfuric acid were added and reacted at 110 ° C. for 4 hours to synthesize porous polymer particles into which sulfonic acid groups had been introduced. Then, normal particles were produced by performing heat drying at 80 ° C. for 1 hour.

[experimental method]
A stainless steel column having a diameter of 7.8 mm and a length of 150 mm was packed under the conditions of a filling solvent of 0.1% by mass phosphoric acid, a slurry concentration of 50% by mass, a filling pressure of 15 MPa, and a filling time of 30 minutes.
Using a packed column, a high-performance liquid chromatograph (L2000, manufactured by Hitachi High-Technologies Corporation) was used as an eluent 0.1 mass% phosphoric acid aqueous solution, column temperature 25 ° C., flow rate 0.5 mL / min, sample 3.5. Chromatographic characteristics were measured under the measurement conditions of mass% formic acid, sample injection amount 2 μL, and eluent UV 210 nm. The number of theoretical plates, column pressure, peak symmetry, and peak shape were determined by chromatographic measurement, and used as indices of particle characteristics.

[Experimental result]
The experimental results are shown in Table 2. In addition, the coverage of the child particles shown in Table 2 was calculated as (surface area of insulating coating portion / total surface area) × 100% by SEM image analysis after 100 particles were taken out from the column after the experiment was completed.

  There were some problems when using normal particles. First, monodisperse particles are difficult to fill because the particles tend to line up. For this reason, the number of theoretical plates does not improve, the column pressure tends to increase, the peak symmetry is poor (1 is optimal), and tailing (peak tailing) tends to occur.

  The core-shell particles 1 to 5 coated with 40% of erythrocyte-shaped particles or potato-like particles gave very good results. This is presumably because the red blood cell shaped particles and potato-like particles are firmly adsorbed to the parent particles and are not easily removed, and they become an appropriate spacer to improve the packing property to the column. As a result, the number of theoretical plates, column pressure, peak symmetry, and peak shape were all improved compared to the case of using normal particles.

  On the other hand, the core-shell particle 6 using the spherical child particles 6 was also slightly inferior to the core-shell particles 1 to 5, but a great improvement effect was obtained. If the child particles are spherical, the child particles are likely to drop off (actually, the coverage is lower than the design), and the child particles are easy to move, so use red blood cell shaped particles or potato shaped particles. Compared to the case, the characteristics tended to deteriorate.

  In the case of the core-shell particle 7 having a child particle coverage of 10% and the core-shell particle 8 having a coverage of 60%, the properties are inferior to those in the case where the coverage is 40%, but improvements in properties are observed compared to the normal particles. It was.

  In the case of the core-shell particle 9 in which the carboxyl group is not introduced into the parent particle, the child particle is dropped, and the property is inferior to that in the case where the carboxyl group is introduced into the parent particle, but the property is improved compared to the normal particle. Admitted.

Claims (10)

  A core-shell type particle for a column, comprising a parent particle and a plurality of child particles attached to the outside of the parent particle.   The core-shell type particle for a column according to claim 1, wherein the child particles are attached to the outside of the parent particles by chemical bonding.   The core-shell type particle for a column according to claim 2, wherein the child particle is attached to the outside of the parent particle through a chemical bond via a polymer.   The core-shell type particle for a column according to any one of claims 1 to 3, wherein a covering ratio of the child particles is in a range of 10 to 70% with respect to a total surface area of the parent particles.   The core-shell type particle for columns according to any one of claims 1 to 4, wherein the child particles are semicircular particles.   The core-shell type particle for columns according to any one of claims 1 to 4, wherein the child particles are spherical particles having irregularities on the surface. A method for producing a core-shell type particle for a column, comprising: a parent particle; and a plurality of child particles attached to the outside of the parent particle;
Adsorbing the polymer electrolyte on the outer side of the parent particles having a functional group;
Adsorbing child particles on the outside of the polymer electrolyte,
A method for producing core-shell type particles for a column.   The method for producing core-shell type particles for columns according to claim 7, wherein the functional group is a carboxyl group.   The method for producing core-shell particles for a column according to claim 7 or 8, wherein the polymer electrolyte is a polyamine.   The method for producing core-shell particles for a column according to any one of claims 7 to 9, wherein the polymer electrolyte is polyethyleneimine.