# US 11,999,808 B2 · Polymer particles with a gradient composition and methods of production thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,999,808 B2 - Document ID: US11999808B2 - Status: Granted - Kind: B2 - Application number: 16/287,364 - Filed: 2019-02-27 - Published: 2019-10-24 - Granted: 2024-06-04 - Earliest claimed: 2018-02-27 - Assignees: Waters Technologies Corporation - Applicants: Waters Technologies Corporation - Inventors: Darryl W. Brousmiche; Kevin Daniel Wyndham; Mingcheng Xu; Michael F. Morris - Web page: https://patentgrep.com/patent/US11999808B2 ## CPC - C08F 2/04: Polymerisation in solution (C08F2/32 takes precedence) - B01J 20/286: Phases chemically bonded to a substrate, e.g. to silica or to polymers - B01J 20/3085: {Chemical treatments not covered by groups B01J20/3007 - B01J20/3078} - B01J 20/3208: {Polymeric carriers, supports or substrates} - B01J 20/3282: {Crosslinked polymers} - B01J 20/3289: {Coatings involving more than one layer of same or different nature} - B01J 20/3293: {Coatings on a core, the core being particle or fiber shaped, e.g. encapsulated particles, coated fibers} - B01J 39/26: Cation exchangers for chromatographic processes - B01J 41/20: Anion exchangers for chromatographic processes - B01J 43/00: Amphoteric ion-exchange, i.e. using ion-exchangers having cationic and anionic groups; Use of material as amphoteric ion-exchangers; Treatment of material for improving their amphoteric ion-exchange properties (ion-exchange chromatography processes B01D15/36) - C08F 2/06: Organic solvent - C08F 212/08: Styrene - C08F 220/20: of polyhydric alcohols or phenols {, e.g. 2-hydroxyethyl (meth)acrylate or glycerol mono-(meth)acrylate} - C08F 220/56: Acrylamide; Methacrylamide - C08F 285/00: Macromolecular compounds obtained by polymerising monomers on to preformed graft polymers - C08K 5/005: {Stabilisers against oxidation, heat, light, ozone} - C08K 5/14: Peroxides - C08K 5/23: Azo-compounds - C08L 39/06: Homopolymers or copolymers of N-vinyl-pyrrolidones - G01N 30/96: using ion-exchange (G01N30/02, G01N30/90 take precedence) - C08F 220/281: {and containing only one oxygen, e.g. furfuryl (meth)acrylate or 2-methoxyethyl (meth)acrylate} - C08L 2205/24: Crystallisation aids - C08L 2207/53: Core-shell polymer - C08F: MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS - B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS - C08K: Use of inorganic or non-macromolecular organic substances as compounding ingredients (paints, inks, varnishes, dyes, polishes, adhesives C09) - C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract The current invention provides a novel method to synthesize a mono-disperse non-porous polymer particles with a unique gradient composition from the core to the shell. In particular, The present invention offers the flexibility to design the chemical and physical properties of different sections of the particle. This flexibility allows for significant latitude in the design of particles for analyzing a large variety of samples in different fields—through using these particles in different chromatography techniques including, but not limited to, ion exchange HPLC (e.g., bio-separation at different modes), reversed-phase HPLC, narrow bore and capillary HPLC, hydrophilic/hydrophobic interaction liquid chromatography, capillary electrochromatography separation, and two dimensional liquid chromatography. ## Claims ### Claim 1 A method of producing monodisperse polymer particles comprising a nucleation step by polymerizing mono-vinyl monomers together with a crosslinking monomer included in an amount of 3 weight percent based on total amount of mono-vinyl monomers to form a low crosslinked nucleus, wherein the crosslinking monomer comprises two or more vinyl groups, and wherein the nucleus contains live reactive sites for further polymerization; a growth step by growing particles from the live reactive sites of the nucleation step by adding a monomer mixture or a sequence of monomer mixtures and varying the sequence, timing, and rate of the monomer mixture additions such that there are no boundaries throughout the grown polymer layers to form a gradient or multiple gradients as a predetermined pattern, wherein the gradient or multiple gradients are chemical and/or physical gradient(s). ### Claim 2 (depends on 1) The method according to claim 1, wherein the monodisperse polymer particles comprise additional live reactive sites for further polymerization. ### Claim 3 (depends on 2) The method according to claim 2 further comprising polymerizing from the additional live reactive sites of the growth step by adding a monomer mixture with different functionality to form monodisperse polymer particles with surface functionality which meets end use application or is suitable for further surface modification. ### Claim 4 (depends on 1) The method according to claim 1, wherein the monodisperse polymer particles comprise of non-porous polymer particles. ### Claim 5 (depends on 1) The method according to claim 1, wherein all the steps are conducted in a homogeneous solvent system. ### Claim 6 (depends on 1) The method according to claim 1, wherein the nucleation step comprises dissolving said mono-vinyl monomers and said crosslinking monomer in an organic solvent. ### Claim 7 (depends on 6) The method according to claim 6, wherein the nucleation step comprises dissolving said mono-vinyl monomers and said crosslinking monomer in an organic solvent and one or more cosolvents. ### Claim 8 (depends on 7) The method according to claim 7, wherein a stabilizer and a radical initiator are further dissolved in the organic solvent. ### Claim 9 (depends on 8) The method according to claim 8, wherein the nucleation step is initiated by heat. ### Claim 10 (depends on 1) The method according to claim 1, wherein the monomer mixture or the sequence of monomer mixtures of the growth step comprises a mono-vinyl monomer. ### Claim 11 (depends on 10) The method according to claim 10, wherein the mono-vinyl monomer is selected from a group consisting of acrylate, methacrylate, acrylamide, methacrylamide, acrylonitrile, styrenes, vinyl esters, vinyl ethers, vinyl halides, vinyl amines, vinyl amide, and a mixture thereof. ### Claim 12 (depends on 10) The method according to claim 10, wherein the monomer mixture or the sequence of monomer mixtures of the growth step further comprises a polyfunctional vinyl monomer. ### Claim 13 (depends on 12) The method according to claim 12, wherein the polyfunctional vinyl monomer is selected from a group consisting of polyfunctional acrylates, methacrylate, aromatic vinyl monomers, and a mixture thereof. ### Claim 14 (depends on 1) The method according to claim 1, wherein the growth step further comprises adding a gradient monomer solution that is modified by alteration of monomer components, alternation of monomer concentrations, or both. ### Claim 15 (depends on 7) The method according to claim 7, wherein the co-solvent is an organic solvent capable of forming a homogenous solvent system with the organic solvent. ### Claim 16 (depends on 15) The method according to claim 15, wherein the co-solvent is cyclohexane, toluene, methylcyclohexane, isooctane, acetonitrile, acetone, ethyl acetate, isopropyl acetate, tetrahydrofuran, methyltetrahydrofuran, a xylene solvent, a glycol solvent or a mixture thereof. ### Claim 17 (depends on 8) The method according to claim 8, wherein the stabilizer is surfactant or a mixture of surfactants. ### Claim 18 (depends on 17) The method according to claim 17, wherein the stabilizer is PVP-40, PVP-360, TRITON N-57® (polyethylene glycol (1,1,3,3-tetramethylbutyl)phenyl ether phosphate), or a mixture thereof. ### Claim 19 (depends on 8) The method according to claim 8, wherein the radical initiator is a peroxide, a peroxyacetate, a persulfate, an azo initiator or a mixture thereof.