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PMMA Microspheres with Embedded Lanthanide Nanoparticles by Photoinitiated Dispersion Polymerization with a Carboxy-Functional Macro-RAFT Agent

Tan, Jianbo, Zhao, Guangyao, Zeng, Zhaohua, Winnik, Mitchell A.
Macromolecules 2015 v.48 no.11 pp. 3629-3640
acrylic acid, binding sites, biotin, chemical bonding, composite polymers, ethanol, fluorescence, fluorides, mass spectrometry, metal ions, microbeads, nanoparticles, polymerization, polymethylmethacrylate, prototypes, serum albumin, spectrometers
Functional poly(methyl methacrylate) (PMMA) microbeads with a very narrow size distribution were synthesized by photoinitiated RAFT dispersion polymerization in aqueous ethanol using an acrylic acid–oligo(ethylene glycol) copolymer as a macro-RAFT agent. These particles are a prototype for multiparameter bead-based assays employing mass cytometry, a technique in which metal-encoded beads are injected into the plasma torch of an inductively coupled plasma mass spectrometer (ICP-MS), and the metal ions generated are detected by time-of-flight mass spectrometry. To label the beads, the polymerization reaction was carried out in the presence of various types of small (ca. 5 nm) lanthanide fluoride (LnF₃) nanoparticles (e.g., LaF₃, CeF₃, and TbF₃) with polymerizable methacrylate groups on their surface. The type of metal ion and the metal content of the PMMA microbeads could be varied by changing the composition of the reaction medium. An important feature of these microbeads is that acrylic acid groups in the corona are available for covalent attachment of biomolecules. As a proof of concept, FITC–streptavidin (FITC-SAv) was covalently coupled to the surface of a Ln-encoded microbead sample. The number of FITC-SAv binding sites on the beads was determined through three parallel assays involving biotin derivatives. Interaction of the beads with a biotin–tetramethylrhodamine derivative was monitored by fluorescence, whereas interaction of the beads with a biotin-DOTA-Lu derivative was monitored both by ICP-MS and by mass cytometry. Each measurement detected an average of ca. 5 × 10⁴ biotins per microsphere. Control experiments with beads covalently labeled with FITC–bovine serum albumin (FITC-BSA) showed only very low levels of nonspecific binding.