Patent ID: 8628822
Filing Date: 2014-01-14
Classification: C03C,C07H,G01N,Y10T

Abstract:
1. A method for preparing a conformal polymer-coated controlled porosity glass (CPG) particle useful for oligonucleotide production, said method being performed in the absence of a coupling agent to link the coating to the substrate of the CPG particle and comprising: (a) cooling CPG particles having pores with a mean average diameter of: 500 Angstroms to 4000 Angstroms (50 nm to 400 nm) to a temperature below about 10° C.; (b) mixing the cooled CPG particles and a cold solution comprising a coating compound and a first solvent, wherein the coating compound is a polymer comprising monomeric subunits or a polymerizable monomer selected from the group consisting of a vinylbenzylchloride, an acrylic, a styrene, polymers thereof, and mixtures thereof; (c) combining the CPG particles and the coating compound solution resulting from the mixture of (b) with a second solvent which differs from the first solvent and a crosslinking agent while maintaining the CPG particles at a temperature below about 10° C.; (d) removing the first solvent from the coating compound solution while retaining the second solvent in the coating compound solution and maintaining the coating compound solution at a temperature below about 10° C.; (e) heating the CPG mixture of (d) which comprises the second solvent to a temperature of about 38° C. to about 65° C. under an inert gas, to permit the crosslinking agent to react with the groups in the monomeric subunits or polymerizable monomers of the coating compound so as to provide the CPG particles with a conformal polymeric coating cross-linked in the range of about 2 to 40%, wherein the crosslinked conformal polymeric coating layer is on the surface of the CPG particle and within its pores without changing the shape of the coated CPG particles, and whereby the conformal coated pores within the conformal coated CPG particles retain an average pore size of at least 90% of the average pore size of the uncoated CPG particles, based on dry pore size, wherein the second solvent has a boiling point higher than the reaction temperature of step (e); (f) cooling the coated CPG particles; (g) washing and drying the coated CPG particles, and (h) derivatizing the conformal coated CPG particles with an amino functional group suitable for nucleoside loading.