Exploiting\nOnline Spatially Resolved Dynamic Light\nScattering and Flow-NMR for Automated Size Targeting of PISA-Synthesized\nBlock Copolymer Nanoparticles

Programmable synthesis of polymer nanoparticles prepared\nby polymerization-induced\nself-assembly (PISA) mediated by reversible addition–fragmentation\nchain-transfer (RAFT) dispersion polymerization with specified diameter\nis achieved in an automated flow-reactor platform. Real-time particle\nsize and monomer conversion is obtained via inline spatially resolved\ndynamic light scattering (SRDLS) and benchtop nuclear magnetic resonance\n(NMR) instrumentation. An initial training experiment generated a\nrelationship between copolymer block length and particle size for\nthe synthesis of poly(<i>N</i>,<i>N</i>-dimethylacrylamide)-<i>b</i>-poly(diacetone acrylamide) (PDMAm-<i>b</i>-PDAAm)\nnanoparticles. The training data was used to target the product compositions\nrequired for synthesis of nanoparticles with defined diameters of\n50, 60, 70, and 80 nm, while inline NMR spectroscopy enabled rapid\nacquisition of kinetic data to support their scale-up. NMR and SRDLS\nwere used during the continuous manufacture of the targeted products\nto monitor product consistency while an automated sampling system\ncollected practically useful quantities of the targeted products,\nthus outlining the potential of the platform as a tool for discovery,\ndevelopment, and manufacture of polymeric nanoparticles.