A Mechanism for Forming Large Fluorescent Organo-Silica Particles: Potential Supports for Combinatorial Synthesis

Abstract

The ability to track multiple compounds through a combinatorial synthesis on solid support particles can be a challenging exercise. A novel solution to this problem is to use the optical characteristics of each support particle to identify the biomolecule synthesized on its surface. To achieve this, we have synthesized a new class of porous, thiol-functionalized supports in a two-step process that used 3-mercaptopropyl trimethoxysilane as the monomer. The monomer was hydrolyzed and polymerized in an acidic solution, which formed an emulsion that was subsequently cross-linked with either ammonia (NH3) or methylamine (CH3NH2). The synthetic process and resulting organo-silica particles were characterized using silicon NMR, scanning electron microscopy techniques, and fluorescence microscopy. Furthermore, thin sections of the porous beads were successfully produced and analyzed via transmission electron microscopy. By controlling the reaction conditions during the synthesis, we achieved a variety of particle morphologies, including hollow particles, particles with macropores on the surface, and particles with a highly porous interior. The mechanism for forming and controlling the morphology of these particles is described here. Also described is the unique process of incorporating fluorescence dyes using combinatorial methods. This enabled the synthesis of a highly optically diverse population of particles, which could be produced over a small number of reactions. Flow cytometry was used to demonstrate the diversity of fluorescence signatures possessed by these encoded particles.