IE911906A1 - Process for the preparation of aqueous dispersions of¹magnetizable polymer particles with a narrow distribution - Google Patents

Description

PROCESS FOR THE PREPARATION OF AQUEOUS DISPERSIONS OF MAGNETIZABLE POLYMER PARTICLES WITH A NARROW DISTRIBUTION The present invention relates to a process for 5 the preparation of aqueous dispersions of magnetizable polymer particles with a narrow distribution from aqueous dispersions of said particles with a wide distribution.

Polymer microspheres are involved in the preparation of diagnostic tests of the radioimmunoassay or immunoenzymatic type; the separation and washing steps are simplified when these microspheres are magnetizable. The efficacy of these microspheres increases as their size distribution becomes narrower; in fact, a good narrowing of the size distribution makes it possible to obtain a sharp sedimentation front and a supernatant phase devoid of fine particles, while at the same time limiting the sedimentation phenomenon due to large particles.

The size monodispersity makes it possible to find out the exact adsorption area of the microspheres and hence their optimum binding capacity in respect of antigens or antibodies.

In a quite different application, namely magneto-thickening fluids based on suspensions of magnetizable polymer particles, the best performance characteristics are achieved when the magnetizable particles have a narrow size distribution.

European patent n° 38730 describes a process for the preparation of magnetizable polymer latices which consists in dispersing the magnetic charge in an organic phase containing an organosoluble initiator and/or the monomer(s), mixing the dispersion with an aqueous solution made up of water and emulsifier, homogenizing the mixture to give droplets of organic phase with a size of between 0.03 and 5 microns, and finally polymerizing said homogenized mixture after the addition of monomer(s) if necessary. The size of the final particles corresponds to that of the droplets.

The homogenization is carried out in a high-shear homogenizer (for example a colloid mill); the distribution of the droplets (and hence of the polymer particles) is a function of the proportion of emulsifier and the ratio organic phase/aqueous phase.

The size distribution of the polymer particles obtained by this process is generally wide.

In the case of a Gaussian distribution with a median diameter of 1 pm, this distribution will be considered to be wide if the relative standard deviation is of the order of 60%, which means that about 2/3 by weight of the particles have a diameter of between 0.4 and 1.6 pm.

Any distribution whose standard deviation is less than or equal to 30%, and preferably of the order of 15 to 25%, will be considered to be narrow.

The object of the invention is therefore to obtain narrow distributions of particles (standard deviation less than or equal to 30%, preferably of the order of 15 to 25% or even of the order of 3 to 5% by increasing the number of fractionations).

The process of the invention, namely the process for the preparation of aqueous dispersions of magnetizable polymer particles with a narrow distribution from aqueous dispersions of said particles with a wide distribution, is characterized in that: a) the amount of water in the aqueous dispersion with a wide distribution is adjusted, if necessary, so that the proportion by weight of magnetizable polymer particles (solids content) is between about 1 and 40%, preferably between about 4% and about 15%, of said dispersion? b) the surfactant concentration of the dispersion obtained in step a) is increased until two phases are obtained: a so-called liquid phase in which the particles are free, and a so-called solid phase in which the particles are associated? c) the two phases are separated? d) steps a), b) and c) are repeated on the solid phase, if appropriate, as many times as is necessary to give an aqueous dispersion with the desired distribution? and e) the aqueous dispersion with a narrow distribution is recovered and diluted, if appropriate, to give the desired solids content.

The starting aqueous dispersions with a wide distribution can be prepared by any known process; there may be mentioned especially the procedures described in European patent n° 38730, French patent application n® 89.04231 of 31.3.1989 and the French patent applications published under the numbers 2.618.084 and 2.624.873.

The particles of the starting aqueous dispersions can have a size distribution of the order of 0.01 to 20 μία and preferably of the order of 0.1 to 3 μία.

Among the polymers of which the magnetizable particles can be made, there may be mentioned organopolysiloxanes as well as polymers derived from monomer(s) immiscible with water (i.e. with a solubility in water of less than 5% by weight).

Among these monomers, there may be mentioned: - vinylaromatic monomers (styrene, vinyltoluene etc.) - alkyl esters of a,0-unsaturated acids (methyl, ethyl etc. acrylates and methacrylates) - unsaturated carboxylic acid esters (vinyl acetate etc.) - vinyl chloride; vinylidene chloride - dienes (butadiene etc.) - monomers containing nitrile groups (acrylonitrile etc.) The monomer composition from which said polymer is derived can additionally contain up to 10% of its weight (preferably up to 4% of its weight) of at least one monomer carrying ionic or reactive groups such as s +* -SO3H, -OSO3H, -NR3, -COOH, -OH, -NH2, -NR2, -CH-CH2, OCH2C1, -CONH2, -SH, -N, -COOR, -PO(OR)2, 0 R being a Ci-C*, preferably Ci-Cg, alkyl radical.

Examples which may be mentioned are: - vinylbenzenesulphonate, sulphoalkyl esters of unsaturated acids (2-sulphoethyl methacrylate etc.) - unsaturated carboxylic acids (acrylic acid, methacrylic acid, maleic acid, itaconic acid etc.) - hydroxyalkyl acrylates or methacrylates (hydroxyethyl, hydroxypropyl etc. acrylate) - aminoalkyl esters of unsaturated acids (2-aminoethyl methacrylate etc.) - acrylamide - vinylbenzyl chloride - glycidyl methacrylate The magnetizable polymer particles contain from 0.5 to 70% by weight (preferably from 5 to 60%) of a magnetic charge whose size is less than 1 pm and preferably between 0.002 and 0.02 pm; of course, the magnetic charge is sufficiently fine to be able to be included in the polymer particles. This magnetic charge can consist for example of: - metals or their alloys, such as: iron, siliceous iron, nickel, cobalt, samarium or their alloys with molybdenum, chromium, copper, vanadium, manganese, aluminium, titanium, neodymium etc.; - iron oxides: Fe3O<, or 7-Fe2O3, pure, combined with one another or mixed with other oxides such as the oxides of cobalt, manganese, zinc, barium and rare earths; - chromium dioxide.

The solids content of the starting aqueous dispersions with a wide distribution is less than 65% by weight; it is generally of the order of 5 to 30% by weight.

The proportion of surfactant in the starting aqueous dispersions with a wide distribution is between 0.1 and 2 times the CMC (critical micellar concentration, i.e. surfactant concentration necessary 15 for the appearance of the first surfactant aggregates, called micelles).

These surfactants, which give the dispersion its stability, can be anionic, cationic, amphoteric or non-ionic.

Among the anionic surfactants, there may be mentioned alkali metal alkylbenzenesulphonates, alkali metal alkylsulphates such as sodium dodecylsulphate, alkali metal alkyl-ether-sulphates, alkali metal alkylaryl-ether-sulphates and alkali metal dioctylsulphosuccinates.

Among the cationic surfactants, there may be mentioned dialkyl (C10-C30)benzyldimethylammonium halides and polyethoxylated quaternary ammonium salts.

Among the amphoteric surfactants, there may be mentioned N-alkyl (C10-C22) betaines, N-alkyl (C10-C22) amidobetaines, alkyl (C10-C22) imidazolines and asparagine derivatives .

Among the non-ionic surfactants, there may be mentioned polyethoxylated fatty acids, sorbitan esters, polyethoxylated sorbitan esters, polyethoxylated alkylphenols, polyethoxylated fatty alcohols, polyethoxylated or polyglycerolated fatty amides and 10 polyglycerolated alcohols and alpha-diols.

The amount of surfactant to be introduced in step b) is that which is necessary to obtain two phases: a liquid phase in which the particles are free, and a solid phase in which the particles are associated.

To obtain such a decantation, it generally suffices to add to the dispersion obtained in step a) an amount of surfactant such that the surfactant concentration reaches 2.5 to 20 times the CMC and is 20 preferably of the order of 2.5 to 10 times the CMC.

The surfactant used can be the same as that (those) in the starting dispersion or any surfactant compatible with the starting surfactant(s). Examples of surfactants have been given above.

The two phases are then separated by any means, e.g. pumping, suction etc., the decantation being accelerated, if appropriate, by a magnetic field.

Operations a), b) and c) are repeated on the separated solid phase, if appropriate, as many times as is necessary to give the dispersion with the desired narrow distribution.

If appropriate, this solid phase is homogenized 5 and diluted with water to give a single-phase dispersion in which the particles are well separated.

The solid phase(s) separated off in this way by the process of the invention have an increasingly narrow distribution. The particle size of the solid phase is measured for example by optical microscopy or with the aid of adapted granulometers.

The narrowness of the distribution is evaluated by means of the degree of polydispersity.

Of course, the liquid phase recovered in c) can be considered to be the starting dispersion of step a) but devoid of the particle population recovered in the solid phase. Consequently, steps b) and c) of the process of the invention can be applied at least once to this liquid phase. The solid phases generated by increasing surfactant concentrations will consist of smaller and smaller particles. This is a consequence of the action of the surfactant and constitutes the basis of the process according to the invention.

In general, the result is achieved by repeating steps a), b) and c) 1 to 8 times (more generally 2 to 5 times) on the fluid phase and/or the solid phase.

The following Examples are given by way of indication and cannot be considered as limiting the scope and the spirit of the invention.

EXAMPLE 1 The aqueous dispersion of magnetic microspheres treated in the present Example is marketed by Rhone-Poulenc under the reference ESTAPOR\® Ml-180/12. The magnetic microspheres are composite particles consisting of polystyrene and magnetic oxide; the proportion of magnetic oxide is of the order of 12% by weight. The particle size distribution is polydisperse with diameters typically of between 0.1 micrometre and 5 micrometers and with about 70% by weight of the microspheres having a diameter of between 1 micrometre and 3 micrometres; the weight-average size is of the order of 1.8 micrometres. a) The dispersion is diluted with deionized water to bring the proportion of particles to about 5% ( % by weight). b) Sodium laurylsulphate (SLS) is then added in a sufficient amount for the SLS concentration of the dispersion, Clr to be 0.02 mol/litre. c) The dispersion is left to stand for about 15 hours, after which time separation of the solid and liquid phases is observed; the solid phase is decanted at the bottom of the container and the liquid phase is gently sucked off.

As soon as step c) is complete, the recovered fluid phase is retreated as in b), the SLS concentration C2 this time being increased to 0.04 mol/litre, and this is then followed by step c) as before.

The cycle of operations b) and c) is repeated a 5 further 2 times on the fluid phase to give an SLS concentration C<, of 0.08 mol/litre.

The solid phase recovered at the end of this last operation is then redispersed in distilled water; the size distribution of the magnetic particles is analyzed with the aid of a Brookhaven\® DCP 1000 centrifugal photosedimentometer marketed by Brookhaven Inst. Corp.

The size distribution curve is shown in Figure 1. Curve a) represents the cumulative weight distribution curve and curve b) represents the weight distribution curve.

It is deduced therefrom that: - the weight-average diameter of the particles is 0.26 μία with a standard deviation of 0.071 pm; and - the degree of polydispersity is 27% (as opposed to 55% for the starting dispersion).

Figure 2, in which the particle size distributions are compared by transmission electron microscopy before fractionation (Figure 2 a) and after fractionation (Figure 2 b), clearly illustrates the efficacy of the process of separation and narrowing of the particle size distribution.

EXAMPLE 2 In this Example, the aqueous dispersion of magnetic microspheres has the reference ESTAPOR\® Ml-070/ 60. The proportion of magnetic oxide is of the order of 60% by weight. The particle size distribution is polydisperse with diameters typically of between 0.05 micrometre and 3 micrometres and with about 70% by weight of the microspheres having a diameter of between 0.3 micrometre and 1 micrometre; the weight-average size is of the order of 0.7 micrometre.

A cycle of operations a), b) and c), similar to that of Example 1, is performed and then repeated 2 times on the fluid phase to give an SLS concentration C3 of 0.06 mol/litre.

The recovered solid phase is redispersed at a solids content of the order of 5% by weight. SLS is added up to a concentration of 0.05 mol/litre.

The suspension is left to stand for 15 hours and the decanted solid phase is recovered and redispersed in distilled water; the size distribution of the magnetic particles is analyzed with the aid of a Brookhaven\® DCP 1000 centrifugal photosedimentometer. The degree of polydispersity is estimated at 35% (as opposed to 50% for the starting dispersion).

EXAMPLE 3 SLS is added to the dispersion recovered at the end of the treatment of Example 2 up to a concentration of 0.06 mol/litre. Operation c) of Example 1 is then carried out; the solid phase is recovered and treated in accordance with operations a) and b) of Example 1 at an SLS concentration of 0.06 mol/litre, and operation c) is then carried out as before in order to recover a solid fraction. This appears iridescent after 48 hours and has the characteristic of diffracting visible light (violet, green and red colours); this is an obvious indication that the fractionated sample of particles has formed colloidal crystals. These colloidal crystals can only be formed when their constituent particles possess a particularly narrow or even monodisperse size distribution. It has thus been proven that the process of the invention makes it possible to obtain a dispersion of monodisperse particles from a dispersion of microspheres with a wide distribution.

Claims (14)

1. A process for the preparation of aqueous dispersions of magnetizable polymer particles with a narrow distribution from aqueous dispersions of said particles 5 with a wide distribution, characterized in that: a) the amount of water in the aqueous dispersion with a wide distribution is adjusted, if necessary, so that the proportion by weight of magnetizable polymer particles (solids content) is 10 between about 1 and 40% of said dispersion; b) the surfactant concentration of the dispersion obtained in step a) is increased until two phases are obtained: a so-called liquid phase in which the particles are free, and a so-called solid phase in 15 which the particles are associated; c) the two phases are separated; d) steps a), b) and c) are repeated on the solid phase, if appropriate, as many times as is necessary to give an aqueous dispersion with the 20 desired distribution; and e) the aqueous dispersion with a narrow distribution is recovered and diluted, if appropriate, to give the desired solids content.

2. A process according to Claim 1, characterized in 25 that the starting dispersion contains particles with a size distribution ranging from 0.01 to 20 μία.

3. A process according to Claim 1 or Claim 2, characterized in that the polymer particles contain from 0.5 to 70% by weight of a magnetic charge.

4. A process according to any one of the preceding claims, characterized in that, in step a), the 5. Proportion by weight of particles ranges from about 4% to about 15% of said dispersion.

5. A process according to any one of the preceding claims, characterized in that the surfactant introduced in step b) is anionic, cationic, amphoteric or 10 non-ionic.

6. A process according to any one of the preceding claims, characterized in that the amount of surfactant introduced in step b) is such that the surfactant concentration reaches 2.5 to 20 times the CMC. 15

7. A process according to Claim 6, characterized in that the amount of surfactant introduced in step b) is such that the surfactant concentration reaches 2.5 to 10 times the CMC.

8. A process according to any one of the preceding 20 claims, characterized in that steps b) and c) are repeated 1 to 8 times on the fluid phase separated off in c).

9. A process according to Claim 8, characterized in that steps b) and c) are repeated 2 to 5 times on the 25 fluid phase separated off in c).

10. A process according to any one of the preceding claims, characterized in that steps a), b) and c) are repeated 1 to 8 times on the solid phase separated off in c) .

11. A process according to Claim 10, characterized in that steps a), b) and c) are repeated from 2 to 5 times on the solid phase separated off in c).

12. A process according to Claim 1 for the preparation of an aqueous dispersion of magnetizable polymer particles with a narrow distribution, substantially as hereinbefore described and exemplified.

13. A process according to Claim 1 for the preparation of an aqueous dispersion of magnetizable polymer particles with a narrow distribution, substantially as hereinbefore described with reference to the accompanying drawings.

14. An aqueous dispersion of magnetizable polymer particles with a narrow distribution, whenever prepared by a process claimed in a preceding claim.