JPS62204501A - Manufacture of magnetic microsphere - Google Patents

Abstract

PURPOSE:To obtain a magnetic microsphere having variable particle diameter, narrow particle size distribution, excellent dispersibility and chemical stability, and high magnetic responsiveness by dispersing ferromagnetic fine particles hydrophobically treated in monomer, dispersively suspending the particles in aqueous solution and thermally polymerizing it. CONSTITUTION:Ferromagnetic fine particles preferably have approx. 150Angstrom of diameter produced by a coprecipitating method. A hydrophobic treatment is performed by adsorbing an unsaturated fatty acid such as oleic acid to the surfaces of the fine particles or further by adsorbing a surfactant thereto. A polymerization initiator is not particularly limited if it is oil soluble radial polymerization initiator. Dispersant for dispersively suspending the monomer in the aqueous solution is preferably aqueous soluble polymer. The suspension is agitated in suspending step or polymerizing step, a low frequency ultrasonic wave is simultaneously irradiated to enhance the dispersing effect. Then, microspheres of 0.1 - several tens mum of diameter can be manufactured, and the size of produced microsphere is varied according to the frequency of the ultrasonic wave.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to a method for producing magnetic microspheres in which fine ferromagnetic particles are included inside polymeric microspheres. More specifically, it has excellent dispersibility in various aqueous solutions and is suitable as a column packing material for magnetic separation and purification of useful substances in solutions, or as a carrier for test reagents for magnetic determination of rare reagents. The present invention relates to a method for effectively producing magnetic microspheres with excellent chemical stability and excellent magnetic responsiveness.

Conventional technology In the past, polymer microspheres manufactured from various natural and synthetic polymers have been widely used as various fillers, colorants, spacers, toners, medical carriers, photonic agents for substance separation, etc.1 ing.

In particular, various synthetic polymer microspheres, including polystyrene, have excellent chemical and dimensional stability, so they can be used, for example, as a liquid chromatography agent or as a separation and purification agent for enzymes and proteins.

Demand for it as a carrier for diagnostic reagents is rapidly increasing.

Also, recently, CaCO3 has been added inside these micros.

Composite microspheres functionalized by blending inorganic powders such as Fe3O4 and TiO2, dyes, or various chemicals are attracting attention, such as conductive paints, electromagnetic shielding paints,
Attempts are being made to apply it to medical magnetic carriers, magnetic phototransfer agents with improved separation functions, and the like.

By the way, magnetic microspheres used as fillers for various columns and medical carriers are manufactured by emulsion polymerization or suspension polymerization. For example, in emulsion polymerization, A surfactant-containing aqueous solution and monomer are mixed and heated to a constant temperature while stirring.
A method of obtaining microspheres by adding an aqueous solution of a polymerization initiator and polymerizing is carried out. By changing the polymerization conditions, the microspheres produced by this method can have a size of 0.1 to 100 μm, which is suitable as a column packing material or a carrier for diagnostic reagents. When producing microspheres, there are drawbacks such as difficulty in infiltrating the ferromagnetic powder into the microspheres during the double polymerization process.

On the other hand, in suspension polymerization, a monomer with a polymerization initiator dissolved in an aqueous or non-aqueous solution containing a dispersant is mixed and heated to a certain temperature while stirring.

It is known how to obtain microspheres. In this case, the ferromagnetic powder is made hydrophobic and dispersed in a non-aqueous solution.
Magnetic microspheres can be produced by adsorbing monomers and then polymerizing them, but there are problems such as poor chemical stability because the ferromagnetic powder is exposed on the surface of the microspheres. Furthermore, the microspheres obtained by aqueous suspension polymerization are too thick, 0.3 to 1.5 silk, and too large to be used as a carrier for diagnostic reagents.

In addition, methods other than emulsion polymerization or suspension polymerization to produce magnetic microspheres include, for example, dispersing magnetite colloids in an aqueous solution of gelatin, adjusting the pH to form microspheres, and then using an aldehyde-based crosslinking agent. There is a method of cine-solubilizing (Japanese Unexamined Patent Publication No. 195161/1982), or a method of mixing magnetite colloid with a water-soluble polymer or protein such as serum albumin, emulsifying it into simiospheres, and heat-treating it to cine-solubilize it. However, when the coating polymer is hydrophilic, the microspheres swell in an aqueous solution and the magnetite contained inside comes into contact with the dispersion medium solution, resulting in a chemical stability problem. There is a problem. Furthermore, when magnetite colloid is directly coated with a polymer, there is a drawback that it is difficult to completely cover the magnetite particles.

Therefore, it has been desired to develop magnetic microspheres that have excellent chemical stability and dispersibility in various water bath liquids and excellent magnetic responsiveness by completely enveloping the ferromagnetic powder inside the microspheres.

Problems to be Solved by the Invention The purpose of the present invention is to respond to the above-mentioned needs by providing microspheres whose particle size can vary within the range of 0.1 μm to several x meters, a relatively narrow particle size distribution, and dispersibility in various aqueous solutions. Another object of the present invention is to provide a method for effectively producing magnetic microspheres with excellent chemical stability and high magnetic responsiveness.

Means for Solving the Problems As a result of extensive research, the inventors of the present invention have developed a solution by dispersing ferromagnetic fine particles that have been hydrophobized with a surfactant or the like in a monomer.
After adding a polymerization initiator, it is dispersed and suspended in an aqueous solution containing a dispersion stabilizer and polymerized by heating.
The inventors have found a way to achieve the above object, and have completed the present invention based on this knowledge.

That is, in the present invention, after uniformly dispersing hydrophobically treated ferromagnetic fine particles in a monomer and adding a polymerization initiator, the particles are dispersed and suspended in an aqueous solution containing a dispersion stabilizer. The present invention provides a method for producing magnetic microspheres, which comprises heating and polymerizing the magnetic microspheres.

The ferromagnetic fine particles used in the method of the present invention preferably have a particle size of about 150 mm, prepared by a coprecipitation method.

The fine particles are generally subjected to hydrophobization treatment so that they can be uniformly dispersed in various monomers. It is applied by further adsorbing a surfactant onto the unsaturated fatty acid adsorption layer.

Regarding the polymerization initiator used in the method of the present invention,
For example, there are no particular limitations as long as it is an oil-soluble radical polymerization initiator such as an organic peroxide such as benzoyl peroxide or an azo initiator such as azobisdimethylvaleronitrile or azobisisobutyronitrile. The polymerization initiator of Kohori et al. may be dissolved in the monomer before dispersing the ferromagnetic fine particles, or it can be dissolved in the monomer after the fine particles are dispersed in the monomer. Good too.

In the method of the present invention, a dispersant is used to disperse and suspend the monomer in which the ferromagnetic fine particles are dispersed in an aqueous solution. Preferred examples include water-soluble polymers such as polyvinyl alcohol, carboxymethyl cellulose, and gelatin.

The particle size of the magnetic microspheres produced by the method of the present invention varies from 0.1 μm to several nanometers depending on the amount of dispersant added, the ratio of the monomer solution to the dispersion medium aqueous solution, and the method of dispersing the monomer during the suspension and polymerization steps. It can be changed up to.

When the monomer is dispersed in the aqueous solution by ordinary mechanical stirring, the stirring speed is 200 to 600 rp.
By changing the above conditions within the range of m, the particle size can be reduced to 0.
Microspheres of 3-1.5 fi are obtained. On the other hand, emitting low-frequency ultrasonic waves at the same time as stirring during the suspension or polymerization process increases the dispersion effect.
Microspheres of several tens of micrometers can be produced. The size of microspheres generated under ultrasonic radiation varies depending on the frequency of the ultrasonic wave, and generally when the ultrasonic wave in the low frequency range is
When the frequency is 00 KHz or less, microspheres having a size within the above range can be obtained.

Polymerization of monomers is carried out at a temperature of usually 60 to 80°C.
This is done by heating for 4 hours or more.

The magnetic microspheres obtained in this way.

After removing unreacted monomers, polymerization initiators, and excess dispersant by washing with a solvent in which the polymer forming the microspheres is insoluble and which dissolves the monomers, the polymers forming the microspheres are dispersed in water to form a suspension. Alternatively, it may be dried and taken out as a powder. In addition, in order to obtain microspheres with uniform particle size, centrifugation
Ordinary classification operations such as filtration using a mesh can be performed.

Effects of the Invention According to the method of the present invention, since the ferromagnetic fine particles are made hydrophobic and dispersed in the monomer, the affinity between the fine particles and the polymer molecular chain is high, and as a result, the ferromagnetic fine particles inside the microspheres are It is possible to produce chemically stable magnetic microspheres that are not easily affected by the pH of the dispersion solvent.

In addition, by emitting low-frequency ultrasonic waves during the suspension process of monomers in an aqueous solution or the polymerization process, microspheres with a size of 0.1 to several 10 μm, which could not be obtained with conventional suspension polymerization, can be obtained. be able to.

The magnetic microspheres obtained by the method of the present invention have excellent dispersibility in various aqueous solutions, are chemically stable, have excellent magnetic responsiveness, and have particle sizes ranging from 0.1 μm to several micrometers. Since it can be adjusted to 1, it is particularly suitable for M as a magnetic photoresist for various columns and a magnetic carrier for diagnostic reagents.

Example Next, the present invention will be explained in more detail with reference to Examples.

Example 1 Styrene monomer 302 purified by vacuum distillation was mixed with hydrophobized magnetite fine particles (ferricolloid) (C-50 (trade name, manufactured by Taiho Kogyo ■) each having a particle size of about 150 mm, and then washed with acetone. 12 (dried powder) was added and dispersed by ultrasonication for 1 hour. In this solution, 0.12 hbendiyl peracid was dissolved to obtain a monomer stock solution.

-10,000, 70 ml of distilled water, Poval PVA-117 (product name, manufactured by Kuraray) 0.501 and Poval pvA-21
7 (trade name, manufactured by Kuraray) was dissolved at 0°02ff to form an aqueous dispersion medium solution.

The monomer stock solution and dispersion medium aqueous solution obtained in this way were placed in a reaction vessel, and argon gas was blown into the reaction vessel for 400 r.
Stirring was performed for 2 hours at pm.

Next, the reaction vessel was stirred at 400 rpm for 5 hours while being kept at 80° C., and then slowly cooled to room temperature while stirring was continued. Next, the obtained suspension of microspheres was poured into about 600 methanol and left overnight while stirring slowly.

This solution was filtered through a filter paper, and the recovered microspheres were dispersed in distilled water, and then classified using a stainless steel mesh to obtain the desired magnetic microspheres.

Example 2 Hydrophobic magnetite 32 was added to purified styrene monomer 309 and dispersed for 1 hour using 45 KHz ultrasonic waves.

Dissolve 0.32 of azobisdimethylvaleronitrile in this solution to make a 7-mer stock solution, and add Poval PVA-1170.5t and Poval PVA7217 to 70% of distilled water.
0.02? was dissolved to obtain an aqueous dispersion medium solution.

The dispersion medium aqueous solution obtained in this way was put into a reaction tank,
The solution was stirred at 400 rpm while radiating ultrasonic waves of 45 KHz, and the monomer stock solution was added to this solution, followed by dispersion at room temperature for 2 hours while blowing argon gas.

The reaction vessel was then kept at 65° C. and stirred at 400 rpm for 5 hours while continuing to be irradiated with ultrasonic waves, and then slowly cooled to room temperature. Approximately 600 td of the obtained microsphere suspension
The mixture was poured into methanol and left to stand overnight while stirring gently. This solution was filtered through a filter paper, and the collected microspheres were dispersed in distilled water, and then classified using a stainless steel mesh centrifuge to obtain the desired magnetic microspheres.

Examples 3 and 4 Magnetic microspheres were obtained in the same manner as in Example 2, except that the magnetite/monomer charging ratio was changed as shown in the attached table.

Example 5 In Example 2, the amount of magnetite/monomer charged was changed to 1.
! Prepare a monomer stock solution instead of IM'/30.

Further, dispersion was carried out for 1 hour at a stirring speed of 200 rpm in the dispersion medium aqueous solution while radiating ultrasonic waves of 45 KHz. Next, the ultrasonic radiation was stopped, the reaction tank temperature was kept at 65°C, and the mixture was stirred at 200 rpm for 5 hours, and then slowly cooled to room temperature.

The obtained microspheres were washed and classified in the same manner as in Example 2 to obtain magnetic microspheres.

Example 6 Azobisdimethylvaleronitrile was dissolved in 0.1 ri. Purified styrene monomer 109 was added to aqueous solution 902 containing the same concentration of dispersant as in Example 2, and dispersion was performed for 2 hours at a stirring speed of 400 rpm while radiating 45 KHz ultrasonic waves.

Next, the ultrasonic radiation was stopped, the reaction tank temperature was kept at '1 (i5°C), and the mixture was stirred at 400 rpm for 5 hours and then slowly cooled to room temperature.

The obtained microspheres were washed and classified in the same manner as in Example 2 to obtain magnetic microspheres.

Example 7 In Example 2, 20 KH2 ultrasound was used, and
Magnetic microspheres were obtained in the same manner as in Example 2, except that the dispersion treatment time before polymerization was changed to 4 hours.

Example 8 Magnetic microspheres were obtained in the same manner as in Example 2, except that 38 KHz ultrasound was used.

The main properties of the magnetic microspheres thus obtained are shown in the attached table.

The intraparticle magnetite content was determined by iron analysis using atomic absorption. In addition, the magnetic sedimentation time is 1200
Place a test tube with an inner diameter of 6n on the G magnet and add 5%
An aqueous suspension of magnetic microspheres was injected to a height of f 5 crs, and the time until all the microspheres settled was measured. However, the value in parentheses is the natural settling time in the absence of magnetism.

Claims (3)

[Claims] 1. It is characterized by uniformly dispersing hydrophobically treated ferromagnetic fine particles in a monomer, adding a polymerization initiator, and then dispersing and suspending them in an aqueous solution containing a dispersion stabilizer, followed by heating polymerization. Method for manufacturing magnetic microspheres. 2. Magnetic microspheres obtained by using mechanical stirring or a combination of mechanical stirring and low-frequency ultrasonic radiation when dispersing and suspending a monomer in which ferromagnetic fine particles are dispersed in an aqueous solution containing a dispersant. A method according to claim 1 for controlling the particle size of. 3. 2. The method according to claim 1, wherein the particle size of the obtained magnetic microspheres is adjusted by using mechanical stirring or a combination of mechanical stirring and low-frequency ultrasonic radiation during heating polymerization.