WO2005026225A1 - Process of making monodisperse, spherical, controlled-size micrometer polymer particles - Google Patents

Abstract

The invention relates to a two-stage process for making monodisperse, spherical, controlled-size, micrometer polymer particles from dispersion polymerization compositions, wherein the obtained particles have a diameter from 1 to 10 mm. In one preferred embodiment, the particles are crosslinked. In another preferred embodiment, the obtained particles comprise a dye, preferably a 330-380 nm absorbing dye attached to the polymer. In a more preferred embodiment, the particles are crosslinked and dyed and have pigment-like properties. The polymer particles provide excellent properties, especially high temperature stability and easy applicability as 330-380 nm absorbing pigments in different standard polymers.

Description

Process of making monodisperse, spherical, controlled-size micrometer polymer particles

This invention relates to a two-stage process for making spherical, controlled-size micrometer polymer particles from dispersion polymerization compositions, wherein the obtained particles have a very narrow or monodisperse size distribution. In the terms of the present invention, a very narrow or monodisperse size distribution pertains to particles in which the coefficient of variation (CV) of particle diameters is preferably less than 5 % and more preferably less than 3 %.

In a preferred embodiment, the invention relates to a two-stage process for making crosslinked, spherical, controlled-size micrometer polymer particles from dispersion polymerization compositions, wherein the obtained particles have a very narrow or monodisperse size distribution. In another preferred embodiment, the obtained spherical, controlled-size micrometer polymer particles further comprise a fluorescent or non-fluorescent dye attached the polymer chain.

In an even further preferred embodiment the invention relates to a two-stage process for making crosslinked and dyed, spherical, controlled-size micrometer polymer particles from dispersion polymerization compositions, wherein the obtained particles have a very narrow or monodisperse size distribution and have pigment-like properties.

Background of the Invention

Recently, there has been a growing interest in monodisperse polymeric beads in the micrometer size range. Therefore several techniques for the preparation of monodisperse beads have been developed and proposed.

Polymer beads (latex particles) with diameters between 40 to 600 nm can be prepared by traditional emulsion polymerization methods developed by the paint industry. Larger diameter beads can be made by precipitation polymerization, seeded polymerization or by activated swelling and polymerization methods. US 5,496,897 (Yoshimatsu et al.) discloses a two-step seeded polymerization process for preparing uniformly sized, fine polymer particles in aqueous dispersions, wherein in a first step a non-ionic organic compound is admixed with an oil-soluble, ethylenically unsaturated monomer and the mixture is added to an aqueous dispersion of seed polymer particles, so as to make the mixture adsorb into the particles. In a second step the polymerization is initiated with an oil-soluble initiator.

EP 0 003 905 and US 4,530,956 (both Ugelstad et al) disclose a two-step process for aqueous dispersion polymerization, wherein in a first step a dispersion of polymer particles containing one or more materials having a very low solubility in water is formed, and, in a second step, a partly water-soluble material is added, which diffuses into the polymer particles obtained in the first step. Where said partly water-soluble material is a polymerizable monomer its polymerization can be effected after diffusion into the polymer particles.

EP 0 326 383 (Okubo et al) discloses a similar process (often referred to as the "dynamic swelling" method) to prepare monodisperse polymer particles having increased particle size in a diameter range around 8.5 μm.

However, all of the above processes for making micrometer diameter polymer particles have limitations. In particular, they are complex and difficult to implement on a large scale.

The invention of the single-step dispersion polymerization process has greatly facilitated the preparation of monodisperse beads with micrometer diameters, making it a very attractive procedure for a large-scale preparation.

Dispersion polymerization is defined as a polymerization reaction in which the monomer is soluble, but the polymer is not. The polymer begins to precipitate as it is formed. Dispersion polymerization differs from precipitation polymerization in that it is carried out in the presence of a second soluble polymer (the dispersant or steric stabilizer). The dispersant becomes attached to the surface of the precipitating polymer formed in the reaction, and forces the precipitate to form micron-sized beads. Thus, unlike emulsion and suspension polymerization, the reaction mixture for dispersion polymerization is a single-phase (a homogeneous liquid), consisting of a solution of monomers, initiator, and steric stabilizer in a solvent that does not dissolve the resultant polymer. The initial stage is believed to occur as a typical solution polymerization. The polymeric chains grow in size until they become insoluble in the reaction medium. The polymer then precipitates from the solution. This step is called the nucleation step. The steric stabilizer forms a graft copolymer and both the graft polymer as well as the ungrafted stabilizer, adsorb on the surface of the particles and prevent their coalescence. Particle growth can then occur by polymerization within the monomer-swollen stabilized particle and by precipitation of polymer formed in the medium onto the growing particle.

A wide variety of monomers have been used in dispersion polymerizations. These include methyl methacrylate, styrene, vinyl acetate, vinyl chloride, acrylamide, acrylic acid, vinylpyrrolidone, acrylonitrile, and 4-chloromethylstyrene. Dispersion polymerization has also been used for the preparation of copolymers of styrene with a variety of different monomers.

One big challenge for dispersion polymerization is the synthesis of polymer particles containing covalently bound fluorescent or non-fluorescent dyes attached to the polymer. There are references in the literature which show, that when dispersion polymerization reactions were carried out in the presence of a dye containing an ethylenically unsaturated copolymerizable functional group, the obtained particles were odd-shaped and had a very broad size distribution.

The biggest challenge for dispersion polymerization however is the synthesis of cross- linked polymer particles. There are many references in the literature which show, that dispersion polymerization failed when cross-linking agents were present. Very often flocculation or coagulation of the product occured or the obtained particles were odd- shaped and had a very broad size distribution.

US 6,346,592 (Saethre et al.) discloses compact and spherical polymer particles with a narrow size distribution and a process for their production. The special precipitation polymerization process is carried out in a polar organic medium (or such medium mixed with water), wherein the medium is a good solvent for the monomer and a poor solvent for the polymer. The disclosed process is a one-stage process, i.e. all ingredients are present when the polymerization is initiated. In US 5,412,048 (Longley et al) discloses a process for producing cross-linked monodisperse polyvinyl polymeric particles of about 1 to 6 μm size, using isopropyl alcohol or isobutyl alcohol as solvents, and by adding the cross-linking polyvinyl monomer in equal batches or continuously during the entire polymerization process. They do not describe the size distribution criteria that correspond to their use of the term "monodisperse."

The term "monodisperse" has been used loosely in both the open literature and the patent literature. Thompson, Rudin and Lajoie (J. Polym. Sci: Part A: Polym Chem, 1995, 33, 345-357) comment that the spread of particle diameters obtained under one set of conditions in their experiments (particles prepared in a mixture of ethanol and toluene), characterized by a volume geometric standard deviation (GSD) of 1.06, while compressed enough to be considered "monodisperse", is not nearly as narrow as that spread of particle diameters obtained under other conditions (particles prepared in ethanol).

Thompson, Rudin and Lajoie (J. Polym. Sci: Part A: Polym Chem, 1995, 33, 345-357) further describe the synthesis of micrometer-size polystyrene particles by dispersion polymerization in ethanol in the presence of small amounts of a mixture of para- and meta-divinyl benzene (DVB) as a crosslinking agent. For reactions that led to monodisperse particles, 0.2 parts by weight of DVB were present in the initial charge. Larger amounts of DVB could be incorporated only if incremental amounts of DVB were added many hours (e.g., 7 h) after the nucleation stage was complete. In this way they obtained monodisperse particles conaining up to 1 wt-% DVB. The particles considered to be monodisperse had GSD values ranging from 1.02 to 1.06.

These same authors described experiments (J. Appl. Polym. Sci. 1996, 59, 2009-2028) in which larger amounts of DVB were incorporated into the particle synthesis recipe as a crosslinker. They added from 1 to 6 parts by weight of DVB based upon the total amount of the monomer, to the reaction 7 hours after the reaction had begun. In this way, they obtained particles with a narrow size distribution, but the particles were not spherical.

Therefore, a process for making spherical, controlled-size micrometer polymer particles from dispersion polymerization compositions, wherein the obtained particles have a very narrow or monodisperse size distribution is of interest in the art. A particular interest in the art is the synthesis of colored, spherical, controlled-size micrometer polymer particles from dispersion polymerization compositions, wherein the obtained particles have a very narrow or monodisperse size distribution. Such particles, in particular fluorescent particles, can be used in medical diagnostic applications.

Another particular interest in the art is the synthesis of cross-linked, colored spherical, controlled-size micrometer polymer particles with pigment like properties, or so called artificial pigments. However, incorporation of colorants in polymer particles is not at all trivial. Colorants not covalently bond in a polymer matrix tend to agglomerate and to crystallise leading to inhomogeneous distribution of colorants within the matrix. Furthermore with non- covalently bond colorants, fading or bleeding of the colorant occurs. In processes wherein crosslinked particles are forced to imbibe dyes from solution, the subsequent shrinking process can lead to distortions in particle shape and to a broadening of the size distribution.

WO 02/066483 discloses copolymer compositions having pigment like properties comprising a fluorescent or non-fluorescent dye attached to a polymer chain by a spacer. WO 02/066483 further discloses a copolymerisation process to obtain latex particles in a diameter range from 50 to 100 nm, by radical initiated suspension (or miniemulsion) polymerisation in water. The disclosed process is a one-stage process. The physical properties of polymer particles highly depend on the structure of the polymerisable moiety and on the process of polymerization. A typical problem of copolymerisation in general is, that each monomer has its own copolymerization parameters, in the extreme not being copolymerizable at all. WO 02/066483 therefore proposes a concept to allow variation of the dye moieties without significantly changing the copolymerization parameters of the dye monomers, by separating the polymerizable moiety and the dye moiety from each other with a spacer. The spacer is further optimized in chain length and nature to enhance the dye properties in the matrix. WO 02/066483 discloses compounds of the general formulae (a) and (b)

wherein R^ is inter alia defined to be substituted or unsubstituted C_3-6 alkylene, C_3-6 alkoxylene or C_6-10 arylene, preferably (CH₂)₂, (CH₂)₆ and (CH₂)₂-O-(CH₂)₂-O-(CH₂)₂.

US 6,001,936 (Barrera et al.) discloses similar structures to (a) with Ri being (CH₂)₂.

In Polymer Journal (1994. 26, 397-402) and Polymer (Korea) (1994, 18, 285-291 ), W.S. Kim et al. discloses the synthesis and fluorescence behaviour of polymers derived from monomers similar to (b) above, obtained by copolymerisation with styrene.

In Bulletin de la Societe Chimique de France (1975, 5-6, 1196-1200), Dreyfus et al. describe the use of the following compound (c) as part of a study on the effects of copolymerisation conditions on the viscosity and molecular weight distribution of styrene dye compounds.

Summary of the Invention

The objective of the present invention is to provide a process of making spherical controlled-size polymer particles from a copolymer composition in dispersion polymerisation. The obtained particles shall be uniform and of regular shape with a diameter of 1 to 10 μm, preferably with a diameter of 2 to 6 μm, and more preferably with a diameter of 2 to 3 μ , with a very narrow or monodisperse size distribution. In the terms of the present invention, a very narrow size distribution pertains to particles in which the coefficient of variation (CV) of particle diameters is less than 10%, preferably less than 5 % and more preferably less than 3 %. A monodisperse size distribution pertains to particles in which the coefficient of variation (CV) of particle diameters is less than 5 %, preferably less than 3 % and more preferably less than 1%.

The coefficient of variation (CV) is defined by the mathematical expression

1 " \D D„

where D_m, is the average diameter of all particles, D, is the diameter of the h particle, and n is the total number of particles counted in the analysis.

A further objective of the present invention is to provide a process of making monodisperse, crosslinked and/or dyed, spherical, controlled-size micrometer polymer particles from a copolymer composition in dispersion polymerisation.

Surprisingly it has been found, that a two-stage process is suitable for making monodisperse spherical controlled-size micrometer particles. This two-stage process allows one to control the desired diameter of the polymer particles within the range of 1 to 10 μm. It also allows the synthesis of particles in which polymerizable dye derivatives can be covalently attached to the polymer chains and it allows one to synthesize crosslinked polymer particles with a diameter from 1 to 10 μm.

In a preferred embodiment of this invention, the crosslinked and dyed final particles have pigment-like properties and contain covalently bound dye monomers with an absorption at 330-380nm.

The invention therefore relates to a process of making monodisperse spherical controlled-size polymer particles comprising the steps of

a) providing a dispersion polymerization composition comprising a monomer or a co- monomer mixture, an alcohol or an alcohol mixture, a polymer dispersant and an initiator, b) reacting the monomer or the co-monomer mixture under normal dispersion polymerization conditions until a stable particle dispersion with a defined number of particles is obtained,

and thereafter

c) growing the particles of step (b) to a size in the micrometer range by adding more monomer solution or more of the co-monorner mixture solution to the reaction and

optionally

d) simultaneously cross-linking and/or dyeing the particles of step (b) by adding a cross-linking agent and/or dye monomer that is soluble in the reaction medium.

In the following (a) and (b) are referred to as the first stage, whereas (c) and (d) are referred to as the second stage.

The important feature of the preferred embodiment of the invention is that the addition of the cross-linking agent and/or the dye monomer is delayed to the second stage. Thereby the number of particles in the system is established in the (sensitive) first stage, without any cross-linking agent or dye monomer being present. Only in the (less sensitive) second stage the polymer particles are grown, cross-linked and/or dyed, simultaneously maintaining a narrow size distribution.

The first stage is considered complete at less than 1% conversion of the monomer present in the initial reaction.

In a further preferred embodiment of the invention, reaction conditions are chosen by adjusting the monomer and polymeric stabilizer concentrations to give particles with a diameter approximately 10% smaller than the desired diameter. Once the reaction has begun and the number of particles has stabilized, an aliquot is removed from the reaction mixture and is tested for particle size and extent of conversion. Based upon this information, a final particle size is calculated for the case of complete conversion. To obtain particles of controlled size, additional monomer is added to the reaction in the second stage. With the additional monomer additional solvent is added optionally to maintain the solvency of the medium. The amount of additional monomer is the amount necessary for the desired/calculated increase in particle diameter.

In another preferred embodiment of the invention, the particles are cross-linked or dyed in the second stage.

In a more preferred embodiment of the invention, the particles are cross-linked and dyed in the second stage.

Without prejudice to the above said, tiny amounts of crosslinker (up to 0.1 % or 0.2 % by weight based on the total amount monomer) can be tolerated in the first stage. The crosslinker will change the particle size, but has only small deleterious effects on the size distribution.

However, in a more preferred embodiment of the invention, no crosslinker at all is tolerated in the first stage.

For the second stage, a preferred class of dye monomers are imides obtained from 1 ,8-naphthalic anhydride or 1 ,4,5,8-tetracarboxylic naphthalene di-anhydride, preferably with an absorption at 330-380 nm, wherein most preferably the dye moiety is separated from the polymerizable moiety by a spacer.

Another possible class of dye monomers are cyanine dyes such as acrylamide derivatives of 5- or 6-aminofluorescein or rhodamine B methacrylate (availble from Polysciences Corp), with an absorption ranging from 450 to 700 nm.

The dye monomers, preferably with an absorption at 330-380 nm, are selected form the group consisting of the compounds with the general formulae (I), (II) and (III)

in which

G is hydrogen or methyl;

X is oxygen or NR' with R' being hydrogen, C_1-6 alkyl, C_6-ιo aryl, (C_6-ι₀) aryl- (C_1-6) alkyl or (C_1-6) alkyl-(C₆-ι₀) aryl, the alkyl and/or aryl radicals optionally being substituted by hydroxyl (-OH), C_1-6 alkoxyl, halogen (-F, -CI, -Br, -I), cyano (-CN), nitro (-N0₂);

Ri is C_1-6 alkyl, C_6-10 aryl, (C_6-10) aryl-(C_1-6) alkyl or (C_1-6) alkyl-(C_6-10) aryl, the alkyl and/or aryl radicals optionally being substituted by hydroxyl (-OH), C_1-6 alkoxyl, halogen (-F, -CI, -Br, -I), cyano (-CN), nitro (-NO₂); R₂ to R₇ are independently of one another, represent hydrogen, hydroxy (-OH), halogen (-F, -CI, -Br, -I), cyano (-CN), nitro (-NO₂), C_1-8 alkyl, C_1-8 alkoxy, C_1-8 alkylthio, -SO₃H, -SO₂Rn, -SOaNRnR^, -CO₂Rn, -CONRnR^, - NHCORn, in which R11 and R12 are independently of one another C_1-8 alkyl optionally substituted by hydroxy (-OH), halogen (-F, -CI, -Br, -I), cyano (-CN), nitro (-NO₂);

R₈ is hydrogen, C_1-6 alkyl, C_6-ιo aryl, (C_6-10) aryl-(C_1-6) alkyl or (C_1-6) alkyl-(C_6-ιo) aryl, the alkyl and/or aryl radicals optionally being substituted by hydroxyl (-OH), C_1-6 alkoxyl, halogen (-F, -CI, -Br, -I), cyano (-CN), nitro (-NO₂). R represents a substituted or unsubstituted annealed aromatic ring system comprising at least one heteroatom in either the first or the second ring or in both, selected from one of the moieties (1 ) to (4).

R₉ to R₁₂ are independently hydrogen, Cι_-8alkyl, C_3-1oalkenyl, phenyl, phenyl-d- ₄alkyl or -COR₁₃ where R-ι₃ is hydrogen, -C(R₁₄)=CH₂, C_1-6alkyl, phenyl, -COOC_1-4alkyl or -NR₁₅R₁₆, where R₁₄ is hydrogen or C_1-4alkyl; R₁₅ is hydrogen, C_1-6alkyl, C_5-6cycloalkyl, phenyl, phenyl-C_1-4alkyl or C_1-12alkylphenyl and R₁₆ is hydrogen or C_1-12alkyl.

The preferred spacer R is a C_2-6 alkylen or C₆.₁₀ arylen, most preferably C₂ alkylen, C₆ alkylen or a C₆ arylen, preferably substituted by nitro, alkoxy or halogen, more preferably substituted by methyloxy or halogen, most preferably substituted by chlorine.

Preferred polymerizable groups are methacrylate ester groups, acrylate ester groups, methacrylamide or acrylamide groups, most preferably methacrylate ester or acrylamide groups.

Most preferred dye monomers are of the general formula (I).

The dye monomers of formulae (I), (II) and (III) are obtained by the condensation of the dicarboxylic anhydride of the respective dye moiety with an amino alcohol or a diamine comprising the respective spacer in a polar aprotic solvent.

wherein A is the 1 ,8 naphthalene core or the 1,4,5,8 naphthalene core as defined in formula (I), (II) and (III) above.

The hydroxy or amino group on the free end of the spacer can be further functionalized under acid or basic conditions with acrylic or methacrylic acid or derivates thereof, such, as the acid chloride. The final product is obtained in high yield.

The general synthesis is shown in the scheme below

wherein A is defined by naphthalene carboxylic anhydride or naphthalene tetracarboxylic dianhydride, Ri, X and G are as defined above.

The first stage of the copolymerization process according to the invention is usually carried out as a radical initiated dispersion polymerisation process in polar and protic solvent (in particular in alcohols such as ethanol, methanol, isopropanol) with an optional organic co-solvent (such as toluene, dichlorobenzene). The preferred polar protic solvent is ethanol.

The purpose of the co-solvent is to help dissolve the dye in the reaction medium. The preferred content of co-solvent (such as toluene, dichlorobenzene) according to the invention is from 0 to 10, more preferably from 0 to 6 and most preferably from 1 to 3 percent by weight based on the total weight of solvent used.

Chain growth monomers suitable for the above process can be acrylate esters, methacrylate esters, styrene, styrene derivatives such as ortho-, meta- or para-methyl styrene, chlorostyrene, vinyl acetate, vinyl chloride, and acrylonitrile. Preferred chain growth monomers are selected from the group consisting of acrylate, methacrylate, styrene or para-methylstyrene, most preferably styrene. Optionally functional monomers can be incorporated into the reaction, preferably in the second stage. These monomers include ethylenically unsaturated carboxylic acids or hydroxy-substituted carboxylate esters, including vinylbenzoic acid, methacrylic acid, itaconic acid, acrylic acid, hydroxyethylacrylate, or hydroxyethylmethacrylate, glycidyl methacrylate, tBoc-protected or other protected derivatives of para-aminostyrene, preferably methacrylic acid, tBoc-protected para-aminostyrene or hydroxyethylmethacrylate. Further functional monomers are ortho, meta-, or para- substitued styrene derivatives, preferably meta- or para-chloromethylstyrene or meta- or para-vinylphenol, or meta- or para-hydroxymethylstyrene, and most preferably, meta- or para-chloromethylstyrene. Further functional monomers are aminoalkyl methacrylates, hydroxyethyl acrylate and hydroxyethyl methacrylate.

The purpose of these monomers is to introduce functional groups, preferably at the particle surface, for the attachment of dyes, antibodies, DNA fragments, nucleic acid oligomers, proteins, peptides, oligosaccharides, or other groups.

The functional momoner or mixture of functional monomers are added in a final addition step, when the conversion of monomer to polymer in the second stage is between 50% and 95% complete, preferably between 60 and 90% complete and most preferably between 70% and 85% complete.

Initiators for the polymerization are oil-soluble initiators. Preferred initiators are lauroyl peroxide, benzoyl peroxide, 2,2'-azobis(iso-butyronitrile) (AIBN) or 2,2'-azobis(2- methylbutyronitrile) (AMBN), most preferably 2,2'-azobis(2-methylbutyronitrile) (AMBN).

The preferred content of initiator is from 1 to 10, more preferably from 1 to 5 and most preferably between 1 and 2 percent by weight based on the total weight of the chain growth monomer.

While, for very long reaction times (e.g., more than one day), one can add incremental amounts of initiator, a particularly preferred feature of the present invention is that the initiator is added only in the first stage of the polymerization process.

Any polymeric dispersant effective for dispersion polymerization in alcohol solvents will work for the process of the present invention. Examples include polyvinylpyrrolidone

(PVP), poly(2-ethyl-2-oxazoline), hydroxypropyl cellulose (HPC), poly(ethylene oxide), or poly(acrylic acid) (PAA). A preferred polymeric dispersant (steric stabilizer) is polyvinylpyrrolidone (PVP). To enhance the colloidal stability of the particles, a nonionic surfactant such as an ethoxylated alkylphenol, or an ionic surfactant such as Aerosol OT, can be added to the reaction mixture. A preferred surfactant is Triton^® X- 305, which is an octylphenol ethoxylate with a mean degree of ethoxylation of 30, and which is available from Union Carbide Corp.

The preferred content of polymeric dispersant is from 10 to 30, more preferably from 15 to 25 and most preferably between 16 and 20 percent by weight based on the weight of the chain growth monomer present in the first stage of the reaction.

It is a preferred feature of the present invention, that if a dye monomer is added, the dye monomer is only added after the polymer particles have formed and their number is established.

The preferred content of the polymerizable dye-monomer in the particles according to the invention is from 0.01 to 10, more preferably from 1 to 5 and most preferably between 2 and 3 percent by weight based on the total weight of the final particles.

It is a particularily preferred feature of the present invention, that if cross-linking agent is added, the cross-linking agent is only added after the polymer particles have formed and their number is established.

The copolymer particles are thereby obtained as monodisperse, fine latex particles of very uniform regular spherical shape wherein the particle diameter deviates with a coefficient of variation (CV) of less than 10%, and preferably less than 5%, and most preferably, less than 3%. The average particle diameter is from 1 to 10 μm, preferably from 2 to 6 μm and most preferably from 2 to 4 μm.

The uniform size and the uniform and regular spherical shape can be clearly seen in the Figures 1 and 2.

Figure 1 shows an optical microscope image of dye-labeled polystyrene particles manufactured according to the process of the invention, containing 1 wt% of NSA- DCAR-MMA (according to example 8). Figure 2 shows a scanning electron microscope (SEM) image of dye-labeled polystyrene particles manufactured according to the process of the invention, containing 1 wt% of NSA-DCAR-MMA (according to example 8).

Figure 3 shows a GPC spectrum (Rl = refractive index, UV = UV absorbance) of dye- labeled polystyrene particles manufactured according to the process of the invention, containing 3.1 wt% of NSA-DCAR-MMA (according to example 9).

Figure 4 shows a GPC spectrum (Rl = refractive index, UV = UV absorbance) of dye- labeled polystyrene particles manufactured according to the process of the invention, containing 1 wt% of NSA-DCAR-MMA (according to example 8).

Figure 5 shows the correlation of the particle volume (proportional to D³) and the amount of styrene added (according to example 3). A total of five aliquots of the same amount of styrene (St) and ethanol was added and the diameter (D) of the paricles was determined. The particle size (particle volume D³) increases linear with the amount of styrene.

Figure 6 shows an optical microscope image of polystyrene particles manufactured according to example 3 at the points where the aliquots of the same amount of styrene (St) and ethanol were added and where the diameters (D) of the paricles were determined. The particle size distribution remains monodisperse.

Figure 7 shows a scanning electron microscope (SEM) image of dye-labeled polystyrene particles manufactured according to the process of the invention, containing 1.35 wt%, 1.55 wt %, 1.85 wt %, 8.1 wt % of NY-E3-NMA (according to example 10)

In a batch mode of the process according to the invention in step (c) and (d) the second stage monomer or co-monomer mixture, the cross-linking agent and/or the dye monomer and optionally additional solvent are added at once.

In a semi-continous mode of the process according to the invention in step (c) and (d) the second stage monomer or co-monomer mixture, the cross-linking agent and/or the dye monomer and optionally additional solvent are added slowly in small amounts. The colored particles according to the invention are suitable as pigments or coloring agents in polymer applications.

The fluorescent particles according to the invention are suitable for biomedical and medical diagnostic applications if functional monomers are introduced in the second stage of the reaction to put reactive functional groups such as carboxylic acid, primary alcohol, or amino groups at the particle surface.

The crosslinked and dyed copolymer particles according to the invention are described to have pigment-like properties and are therefore referred to as copolymer pigments in the following:

The copolymer pigments according to the invention are suitable for the mass pigmentation of substrates including synthetic polymers, synthetic resins and regenerated fibers optionally in the presence of solvents. These substrates more particularly include oil, water and solvent based surface coatings, polyester spinning melts, polyethylene, polystyrene and polyvinyl chloride melts, polymethacrylate and polymethylmethacrylate melts, polyurethane masses, rubber and synthetic leather. Furthermore, the pigments can be used in the manufacture of printing inks, for the mass coloration of paper and for coating and printing textiles.

The copolymer pigments according to the invention are also suitable as pigments in electrophotographic toners and developers, such as one- or two-component powder toners (also called one- or two-component developers), magnetic toners, liquid toners, polymerization toners and specialty toners.

Typical toner binders are addition polymerization, polyaddition and polycondensation resins, such as styrene, styrene-acrylate, styrene-butadiene, acrylate, polyester and phenol-epoxy resins, polysulphones, polyurethanes, individually or in combination, and also polyethylene and polypropylene, which may comprise further constituents, such as charge control agents, waxes or flow assistants, or may be modified subsequently with these additives.

The copolymer pigments according to the invention are suitable, furthermore, as colorants in powders and powder coating materials, especially in triboelectrically or electrokinetically sprayable powder coating materials which are used for the surface coating of articles made, for example, from metal, wood, plastic, glass, ceramic, concrete, textile material, paper or rubber.

Powder coating resins that are typically employed are epoxy resins, carboxyl- and hydroxyl-containing polyester resins, polyurethane resins and acrylic resins, together with customary hardeners. Combinations of resins are also used. For example, epoxy resins are frequently employed in combination with carboxyl- and hydroxyl-containing polyester resins. Typical hardener components (as a function of the resin system) are, for example, acid anhydrides, imidazoles and also dicyanodiamide and its derivatives, blocked isocyanates, bisacylurethanes, phenolic and melamine resins, triglycidyl isocyanurates, oxazolines and dicarboxylic acids.

The following examples illustrate the invention. Unless otherwise specified, parts and percentages used in the examples are on a weight to weight basis.

Examples

The particle size in the examples is examined by optical microscopy and scanning electron microscopy (SEM). The molecular weight and molecular weight distribution are determined by gel permeation chromatography (GPC). The dye content is determined by UV-VIS absorption measurements or, for soluble polymers, by GPC coupled with UV-VIS detection.

Example 1 : Synthesis of NSA-DCAR-MMA dye monomer Naphthalene carboxylic anhydride (10 parts) is condensed to 2,5-dichloro- paraphenylenediamine (18 parts) at 130°C under nitrgogen atmosphere in presence of catalytic p-toluene sulfonic (0.1 part) acid in dimethylformamide (50 parts). After reaction completion at same temperature, the resulting mixture is cooled to room temperature. After filtration and washing with 50 parts of methanol, the cake is dried under vacuum for 4 hours. The product (18 parts) is then suspended in 100 parts of toluene in presence of 5.6 parts of triethylamϊne at 80°C. 5.8 parts of methylmethacryloyl chloride are then added over 30 minutes to the suspension and the whole reaction mixture stirred for 4 hours at 90°C. After reaction completion, reaction mixture is cooled to 60°C, filtered and washed with 30 parts of methanol and 30 parts of water. After drying, the final dye monomer is obtained with 95% yield (20 parts) as a colorless product.

NMR ¹H (dmso-d₆): 9.0 (s, 1H, NHCO), 8.6 - 7.8 (m, 8H, H arom), 6.0 (s, 1 H, CH), 5.6 (s, 1 H, CH), 2.0 (s, 3H, CH₃); MS (negative mode): 425 (M-); UV (λmax - ε): 350.5 nm - 14000 l/mol.cm

Example 2: Synthesis of NTCA-C2-M MA dye monomer 10 parts of naphthalene tetracarboxylic dianhydride are suspended into 100 parts dimethylformamide in presence of 4.6 parts of 2-ethanolamine and p-toluenesulfonic acid (0.1 part). The mixture is then heated to 90°C and stirred until reaction completion. The resulting colorless solution is cooled to room temperature and filtered. The presscake is then washed with methanol and dried. 12.5 parts of colorless powder are obtained (yield 94%). The product is then suspended into 75 parts of o- dichlorobenzene in presence of 7.5 parts of triethylamine and heated to 90°C. Methylmethacryloyl chloride (7.8 parts) are added over 45 minutes and the reaction mixture is stirred at this temperature for 5 hours. After reaction completion, the mixture is cooled to room temperature, filtered and washed with 50 parts of methanol and then with 50 parts of water. Product is dried and obtained in 95% yield (16.3 parts) as a colorless compound.

NMR ¹H (dmso-d₆): 7.8 - 7.4 (m, 4H, H arom), 5.85 (s, 2H, 2 CH), 5.5 (s, 2H, 2 CH), 4.1 (t, 4H, 2 CH₂), 3.6 (t, 4H, 2 CH₂), 1.8 (s, 6H, 2 CH₃); MS (negative mode): 490 (M-); UV (λmax - ε): 357.0 nm - 6000 l/mol.cm Example 3: Synthesis of size-controlled monodisperse polystyrene particles with different sizes (two stage process)

To a 3 neck 250 mL round bottom flask equipped with a condenser and a gas inlet, monomer styrene (6.25 g), stabilizer polyvinylpyrrolidone PVP (2.0 g), co-stabilizer Triton X-305 (0.7 g), initiator 2,2'-azobis(2-methylbutyronitrile) AMBN (0.25 g), and ethanol (18.75 g) were added. The mixture was stirred at room temperature until a complete solution appeared and was then deoxygenated by bubbling nitrogen for 30 minutes. The solution was then heated to 70°C and mechanically stirred at 100 rpm. This is the starting point of the polymerization process. After 30 minutes at this temperature, the reaction mixture became milky. At this point, 6.25 g styrene in ethanol (19 g) was added to the reaction mixture at 70°C under a nitrogen atmosphere over 10 minutes. After the polymerization reaction was carried out at 70°C for 17 hours, an aliquot was removed for analysis. This aliquot yielded monodisperse particles with diameter of 2.3 μm (CV = 1.3 %). Then an additional amount of styrene (6.25 g) in ethanol (19 g) was added to the reaction mixture at 70°C under nitrogen atmosphere over 10 minutes. After another 23 h of reaction (total reaction time, 40 h), one-third of the reaction mixture was removed from the flask. This sample contained monodisperse particles with diameter of 2.8 μm (CV= 1.2 %). To the remaining reaction mixture at 70°C, 6.25 g styrene in ethanol (19 g) was added under a nitrogen atmosphere over 10 minutes. After the polymerization reaction was carried out for an additional 6 h at 70°C (total reaction time 46 h), an aliquot was removed for analysis. This sample contained monodisperse particles with a diameter of 3.0 μm (CV = 2.2%). To the remaining reaction mixture, 6.25 g styrene in ethanol (19 g) was added at 70°C under nitrogen atmosphere over 10 minutes. The reaction was continued for an additional 22 h (total reaction time 68 h). The reaction was stopped. It contained monodisperse particles with a diameter of 3.3 μm (CV = 2.2 %).

Comparative Example 4: Synthesis of monodisperse polystyrene particles (one stage process according to the prior art)

To a 3 neck 250 mL round bottom flask equipped with a condenser and a gas inlet, monomer styrene (12.5 g), stabilizer polyvinylpyrrolidone PVP (2.0 g), co-stabilizer Triton X-305 (0.7 g), initiator 2,2'-azobis(2-methylbutyronitrile) AMBN (0.25 g), and ethanol (38 g) were added. The mixture was stirred at room temperature until a complete solution appeared and was then deoxygenated by bubbling nitrogen for 30 minutes. The solution was then heated to 70°C and mechanically stirred at 100 rpm. This is the starting point of the polymerization process. After 30 minutes at this temperature, the reaction mixture became milky. After the polymerization reaction was carried out at 70°C for 24 hours, an aliquot was removed for analysis. This aliquot yielded monodisperse particles with diameter of 2.0 μm (CV = 1.3 %).

Comparison of example 3 and 4

In the first part of example 3 (dispersion polymerization separated into two stages, a "nucleation stage" and a "particle growing stage") only half of the styrene and ethanol were added at the beginning of the dispersion polymerization together with the stabilizer (PVP), the co-stabilizer (Triton X-305) and the initiator (AMBN). In example 4 (dispersion polymerization in one stage) the full amount of the styrene and ethanol were added at the beginning of the dispersion polymerization together with the stabilizer (PVP), the co-stabilizer (Triton X-305) and the initiator (AMBN).

As the results clearly show, the particle size obtained in the two stage process as of the invention (example 3) is larger than in the one-stage process of example 4, where all the reactants are added initially to the reaction mixture.

Example 3 (continued)

Example 3 was continued to further increase the size of the particles. Before most of the monomer added in the second stage had reacted, another aliquot containing the same amount of styrene and ethanol was added to the reaction. No additional initiator or PVP was added at this stage. As the reaction continued, the particle size continued to increase. The beads remained colloidally stable in the solution. A total of five aliquots of the same amount of styrene and ethanol was added. The particle size continued to increase.

If no new particles are formed (no secondary nucleation) the particle volume (proportional to D³) should increase linearly with the amount of styrene added. In the above example it was found, that the reaction followed this prediction (see Figure 5). In addition, it was found that the particle size distribution remained very narrow (see Figure 6). Example 5: Synthesis of size-controlled crosslinked monodisperse polystyrene particles (DVB = 1.0 wt%) (two-stage process)

To a 3 neck 250 mL round bottom flask equipped with a condenser and a gas inlet, monomer styrene (12.5 g), stabilizer polyvinylpyrrolidone PVP (2.0 g), surfactant co- stabilizer Triton X-305 (0.7 g), and ethanol (37.5 g) were added. The mixture is stirred at room temperature until a complete solution appears and is then deoxygenated by bubbling nitrogen for 30 minutes. The solution is then heated to 70°C and mechanically stirred at 100 rpm rate. This is the starting point of the polymerization process. A solution of initiator 2,2'-azobis(2-methylbutyronitrile) AMBN (0.25 g) in ethanol is then added. The reaction mixture is stirred for 2 hours. A solution of divinylbenzene (DVB, 0.13 g) in ethanol (30g) is then added at 70°C under nitrogen atmosphere over a time period of 12 hours. After 24 hours of reaction, monodisperse polymer particles were obtained with a diameter of 4.0 μm (CV = 2.5%). No purification of the obtained polymer particles is required.

Example 6: Synthesis of size-controlled crosslinked monodisperse polystyrene particles (DVB = 3.0 wt%) (two-stage process)

To a 3 neck 250 mL round bottom flask equipped with a condenser and a gas inlet, monomer styrene (12.5 g), stabilizer Polyvinylpyrrolidone PVP (2.0 g), surfactant co- stabilizer Triton X-305 (0.7 g), AMBN (0.25 g), and ethanol (37.5 g) were added. The mixture is stirred at room temperature until a complete solution appears and is then deoxygenated by bubbling nitrogen for 30 minutes. The solution is then heated to 70°C and mechanically stirred at 10O rpm. This is the starting point of the polymerization process. The reaction mixture is stirred for 2 hours. A solution of divinylbenzene (DVB, 0.375 g) in ethanol (30g) is then added at 70°C under nitrogen atmosphere over a time period of 12 hours. After 24 hours of reaction, monodisperse polymer particles were obtained with a diameter of 2.3 μm (CV = 3.2%). No purification of obtained polymer particles is required. Comparative Exam ple 7: Synthesis of crosslinked polydisperse polystyrene particles according to the prior art (one-stage process)

To a 3 neck 250 mL round bottom flask equipped with a condenser and a gas inlet, monomer styrene (12.0 g), stabilizer Polyvinylpyrrolidone PVP (4.0 g), surfactant co- stabilizer Triton X-3O5 (0.72 g), AIBN (0.6 g), DVB (0.04 g, 0.35 wt% to monomer), and ethanol (79.0 g) were added. The mixture is stirred at room temperature until a complete solution appears and is then deoxygenated by bubbling nitrogen for 30 minutes. The solution is then heated to 70°C and mechanically stirred at 100 rpm rate. This is the starting point of the polymerization process. After 24 hours of reaction, polydisperse particles were obtained with diameters ranging from 0.6 - 2 μm (CV = 14.5 %). With 0.67 wt% of DVB, the particles are not spherical. With a higher DVB content, flocculation occurred after 5 minutes, and the amount of aggregates increased during the polymerization.

Example 8: Synthesis of size-controlled dyed monodisperse particles of PS-co-(1 wt%-NSA-DCAR- A) polymer (two-stage process)

To a 3 neck 250 m L round bottom flask equipped with a condenser and a gas inlet, monomer styrene (6.25 g), stabilizer polyvinylpyrrolidone PVP (1.0 g), co-stabilizer Triton X-305 (0.7 g), initiator 2,2'-azobis(2-methylbutyronitrile) AMBN (0.25 g) and ethanol (19 g) were added. The mixture is stirred at room temperature until a complete solution appears and is then degassed by bubbling nitrogen for 30 minutes. The solution is then heated to 70°C. After 30 minutes at this temperature, the reaction mixture becomes a milky medium. A hot prepared solution (70°C) of styrene (6.25 g) and NSA-DCAR-MMA dye (0.141 g) [as obtained from example 1] in ethanol (19 g) is added to the reaction mixture at 70°C under nitrogen atmosphere over 10 minutes. Copolymerization of dye and styrene was carried out at 70°C for 24 hours. The copolymer particles formed spontaneously during the polymerization reaction. No purification of obtained polymer particles is required. Properties - Shape and colour: 2.5 μm (CV = 0.4%) sized, monodisperse spherical particles; white latex powder. - Solubility: insoluble in the following solvents: water, methanol, ethanol, acetone; soluble in chloroform, tetrahydrofuran (THF), N,N-dimethyformamide (DMF). Composition: By UV absorption spectroscopy measurements, the product contains 1 wt% of NSA-DCAR-MMA and 99 wt% of styrene. for optical microscope and scanning electrone microscope (SEM) image see Figure 1 and Figure 2

Example 9: Synthesis of size-controlled dyed monodisperse particles of PS-co-(3.1 wt%-NSA-DCAR-MMA) polymer (two-stage process)

To a 3 neck 250 mL round bottom flask equipped with a condenser and a gas inlet, monomer styrene (6.25 g), stabilizer Polyvinylpyrrolidone PVP (1.0 g), co-stabilizer Triton X-305 (0.7 g), initiator 2,2'-azobis(2-methylbutyronitrile) AMBN (0.25 g) and ethanol (19 g) were added. The mixture is stirred at room temperature until a complete solution appears and is then degassed by bubbling nitrogen for 30 minutes. The solution is then heated to 70°C. After 30 minutes at this temperature, the reaction mixture becomes a milky medium. A hot prepared solution (70°C) of styrene (6.25 g) and NSA-DCAR-MMA dye (0.391 g) [as obtained from example 1] in ethanol (19 g) is added to the reaction mixture at 70°C under nitrogen atmosphere over 10 minutes. Copolymerization of dye and styrene was carried out at 70°C for 24 hours. As most part of the dye monomer is not dissolved, a mixture of ethanol / dichlorobenzene (respectively 18.5 g / 4.1 g) is added at 70°C. The reaction mixture is stirred at this temperature for further 17 hours. The copolymer particles formed spontaneously during the polymerization reaction. No purification of obtained polymer particles is required.

Properties Shape and colour: 3.2 μm (CV = 3.2%) sized, monodisperse, spherical particles; white latex powder. Solubility: insoluble in the following solvents: water, methanol, ethanol, acetone; soluble in chloroform, tetrahydrofuran (THF), N,N-dimethyformamide (DMF). - Composition: By UV absorption spectroscopy measurements, the product contains 3 wt% of NSA-DCAR-MMA and 97 wt% of styrene. The process for the synthesis of dye-labeled polystyrene particles according to examples 8 and 9 can be summarized in the following table.

Comparative Example 10: Synthesis of dyed polydisperse particles of PS-co- (HY-E3-NMA) polymer according to the prior art (one-stage process)

HY-E3-NMA is

To a 3 neck 150 mL round bottom flask equipped with a condenser and a gas inlet, 0.018 g (0.46 wt % to styrene) HY-E3-NMA is dissolved in 26.1 g ethanol. 1.27 g PVP, 0.32 g Triton N-20 and 1.1 g styrene are added to the flask and then the flask was placed in an oil bath. The solution was deoxygenated by bubbling nitrogen, heated to the reaction temperature 80 °C, and stirred mechanically at 100 rpm. When the reaction mixture reached the reaction temperature, a solution of 0.15 g AIBN dissolved in 2.1 g styrene (AIBN/styrene = 7 wt%) is deoxygenated and added to the reaction flask. The solution became cloudy in few minutes and became milky in 0.5 h. After the polymerization of styrene was carried out at 80°C for 40 hours. Particles with a relatively narrow size distribution were obtained with mean diameter of 1.3 μm (CV = 6.8 %).

Increased amounts of HY-E3-NMA (1.35 wt %, 1.55 wt %, 1.85 wt %, 8.1 wt %) were used in the same procedure. Polydisperse polymer particles were obtained. Scanning electron microscopy images of these particles are shown in Figure 7.

Claims

Claims

A process of making monodisperse spherical controlled-size micrometer polymer particles comprising the steps of a) providing a dispersion polymerization composition comprising a monomer or a co-monomer mixture, an alcohol or an alcohol mixture, a polymeric dispersant and an initiator, b) reacting the monomer or the co-monomer mixture under normal dispersion polymerization conditions until a stable particle dispersion with a defined number of particles is obtained, and thereafter c) growing the particles of step (b) to a size in the micrometer range by adding more monomer or more of the co-monomer mixture and optionally more solvent to the reaction and optionally d) simultaneously cross-linking and/or dyeing the particles of step (b) by adding a cross-linking agent and/or a dye monomer.

2. A process according to claim 1 , wherein the initial monomer or initial co- monomer mixture is selected from the group consisting of acrylate esters, methacrylate esters, styrene, styrene derivatives such as ortho-, meta- or para- methyl styrene, chlorostyrene, vinyl acetate, vinyl chloride, and acrylonitrile. Preferred chain growth monomers are selected from the group consisting of acrylate, methacrylate, styrene or para-methylstyrene, most preferably styrene.

3. A process according to claim 1 wherein in step (a) the polymeric dispersant is polyvinylpyrrolidone, poly(2-ethyl-2-oxazoline), hydroxypropyl cellulose, poly(ethylene oxide), or poly(acrylic acid), preferably polyvinylpyrrolidone.

A process according to claim 1 wherein in step (a) the initiator is selected from the group lauroyl peroxide, benzoyl peroxide, 2,2'-azobis(iso-butyronitrile) (AIBN) or 2,2'-azobis(2-methylbutyronitrile) (AMBN), preferably 2,2'-azobis(2- methylbutyronitrile) (AMBN)

A process according to claim 1 , wherein in step (c) the second-stage monomer or co-monomer mixture is added after 1 to 95% conversion of the first-stage monomer or monomer-mixture, preferably after 2 to 70% conversion.

A process according to claim 1 , wherein in step (c) the second stage monomer or co-monomer mixture is different from the first stage monomer or co-monomer mixture of step (a).

7. A process according to claim 1 , wherein the cross-linking agent in step (d) is selected from the group consisting of divinylbenzene, ethylene glycol dimethacrylate, butylene glycol dimethacrylate, 1 ,6-hexanediol dimethacrylate, ethylene glycol diacrylate, butylene glycol diacrylate, and 1 ,6-hexanediol diacrylate.

8. A process according to claim 1 or 7, wherein in step (d) the dye monomer is selected from the group consisting of compounds of formula (I), (II) and (III)

in which

G is hydrogen or methyl;

X is oxygen or NR' with R' being hydrogen, C_1-6 alkyl, C_6-10 aryl, (C_6-ιo) aryl-(C_1-6) alkyl or (Cι_-6) alkyl-(C₆-ιo) aryl, the alkyl and/or aryl radicals optionally being substituted by hydroxyl (-OH), C_1-6 alkoxyl, halogen (- F, -CI, -Br, -I), cyano (-CN), nitro (-NO₂);

Ri is C_1-6 alkyl, C_6-ιo aryl, (C_6-10) aryl-(C_1-6) alkyl or (C_1-6) alkyl-(C_6-10) aryl, the alkyl and/or aryl radicals optionally being substituted by hydroxyl (-OH), C_1-6 alkoxyl, halogen (-F, -CI, -Br, -I), cyano (-CN), nitro (-NO₂);

R₂ to R₇ are independently of one another, represent hydrogen, hydroxy (- OH), halogen (-F, -CI, -Br, -I), cyano (-CN), nitro (-NO₂), C_1-8 alkyl, d. ₈ alkoxy, C_1-8 alkylthio, -SO₃H, -SO₂Rn, -SOzNRnR^, -COzRn, - CONRnR₁₂, -NHCORn, in which R11 and R12 are independently of one another C_1-8 alkyl optionally substituted by hydroxy (-OH), halogen (-F, -CI, -Br, -I), cyano (-CN), nitro (-NO₂); R₈ is hydrogen, C_1-6 alkyl, C_6-10 aryl, (C_6-ιo) aryl-(C_1-6) alkyl or (C_1-6) alkyl- (C_6-ιo) aryl, the alkyl and/or aryl radicals optionally being substituted by hydroxyl (-OH), C_1-6 alkoxyl, halogen (-F, -CI, -Br, -I), cyano (-CN), nitro (-NO₂). R_g represents a substituted or unsubstituted annealed aromatic ring system comprising at least one heteroatom in either the first or the second ring or in both, selected from one of the moieties (1) to (4)

Rg to R₁₂ are independently hydrogen, C_1-8alkyl, C_3-10alkenyl, phenyl, phenyl-C-i. ₄alkyl or -COR₁₃ where R-ι₃ is hydrogen, -C(R₁₄)=CH₂, C_1-6alkyl, phenyl, -COOC_1-4alkyl or -NRι₅R₁₆, where R₁ is hydrogen or C_1- alkyl; R₁₅ is hydrogen, Cι_-6alkyl, C_5-6cycloalkyl, phenyl, phenyl-Cι_-4alkyl or Cι_-12alkylphenyl and R ₆ is hydrogen or C_1-12alkyl.

9. A process according to claim 8, wherein the dye monomer is selected from the group consisting of compounds of formula (I) and (II)

wherein R-i is C₂-C₆ alkylen or C_6-10arylen; R₂ to R₇ are chlorine, methoxy, nitro or cyano groups; R₈ is C C₆ alkyl.

10. A process according to claim 8 or 9, wherein the total amount of dye monomer is from 0.01 to 10 percent by weight, preferably from 1 to 5 percent by weight, most preferably from 2 to 3 percent by weight based on the total weight of the final particles.

11. A process according to claims 1 to 10, wherein in step (c) and (d) the second stage monomer or co-monomer mixture, the cross-linking agent and/or the dye monomer and optionally additional solvent are added at once (batch mode).

12. A process according to claims 1 to 10, wherein in step (c) and (d) the second stage monomer or co-monomer mixture, the cross-linking agent and/or the dye monomer and optionally additional solvent are added slowly in small amounts (semi-continous mode).

13. A process according to claims 1 to 10, wherein a functional momoner or mixture of functional monomers is added in a final addition step, when the conversion of monomer to polymer in the second stage is between 50% and 95% complete, preferably between 60 and 90% complete and most preferably between 70% and 85% complete.

14. A process according to claim 13, wherein the functional momoner is chosen from the class of ethylenically unsaturated carboxylic acids or hydroxy- substituted carboxylate esters, including vinylbenzoic acid, methacrylic acid, itaconic acid, acrylic acid, hydroxyethylacrylate, or hydroxyethylmethacrylate, glycidyl methacrylate, tBoc-protected or other protected derivatives of para- aminostyrene, preferably methacrylic acid, tBoc-protected para-aminostyrene or hydroxyethylmethacrylate.

15. A process according to claim 13, wherein the functional momoner is chosen from the class of ortho, meta-, or para-substitued styrene derivatives, preferably meta- or para-chloromethylstyrene or meta- or para-vinylphenol, or meta- or para-hydroxymethylstyrene, and most preferably, meta- or para- chloromethylstyrene.

16. Monodisperse, spherical controlled-size particles particles as obtained by the process according to claims 1 to 15 wherein the size of the particles is in a diameter range from 1 to 10 μm, preferably from 2 to 6 μm, and most preferably from 2 to 4 μm.

17. Monodisperse, spherical controlled-size particles particles according to claim 16, wherein the total amount of dye monomer is from 0.01 to 10 percent by weight, based on the total weight of the final particles, preferably 1 to 5 percent by weight and most preferably 2 to 3 percent by weight.

18. Use of the monodisperse spherical controlled-size particles according to claims 16 or 17 as pigments or coloring agents in polymer applications.

19. Use of the monodisperse spherical controlled-size particles according to claims 16 or 17 as pigment for the attachment of attachment of dyes, antibodies, DNA fragments, nucleic acid oligomers, proteins, peptides, oligosaccharides, or other groups useful for diagnostic or sensor applications. 1/4

Figures

Figure 1: Optical microscope image of dye-labeled polystyrene (PS) particles manufactured according to the process of the invention (containing 1 wt% of NSA-DCAR-MMA) according to example 8

10 μm

Figure 2: SEM image of dye-labeled polystyrene (PS) particles manufactured according to the process of the invention (containing 1 wt% of NSA-DCAR-MMA) according to example 8

2/4

Figure 3: GPC traces of dye-labeled PS particles (3.1 wt %) according to example 9

Volume (ml)

Figure 4: GPC traces of dye-labeled PS particles (1 wt %) according to example 8

Volume, ml Figure 5: Effect of styrene amount added in successive stages on particle size in ethanol according to example 3

St amount (g)

Figure 6: Optical microscopy pictures of polystyrene particles obtained after x h according to example 3. The marker bar is 10μm.

20

46 h 68 h 4/4

Figure 7. SEM images of dyed particles of PS-co-(HY-E3-NMA) polymer with different dye contents according to example 10

0.5 wt% 1.35 wt% 1.55 wt% 1.85 wt% 8.1 wt% (D=1.3 μm, CV=6.8%)