Exploiting Online Spatially Resolved Dynamic Light Scattering and Flow-NMR for Automated Size Targeting of PISA-Synthesized Block Copolymer Nanoparticles

Programmable synthesis of polymer nanoparticles prepared by polymerization-induced self-assembly (PISA) mediated by reversible addition–fragmentation chain-transfer (RAFT) dispersion polymerization with specified diameter is achieved in an automated flow-reactor platform. Real-time particle size and monomer conversion is obtained via inline spatially resolved dynamic light scattering (SRDLS) and benchtop nuclear magnetic resonance (NMR) instrumentation. An initial training experiment generated a relationship between copolymer block length and particle size for the synthesis of poly(N,N-dimethylacrylamide)-b-poly(diacetone acrylamide) (PDMAm-b-PDAAm) nanoparticles. The training data was used to target the product compositions required for synthesis of nanoparticles with defined diameters of 50, 60, 70, and 80 nm, while inline NMR spectroscopy enabled rapid acquisition of kinetic data to support their scale-up. NMR and SRDLS were used during the continuous manufacture of the targeted products to monitor product consistency while an automated sampling system collected practically useful quantities of the targeted products, thus outlining the potential of the platform as a tool for discovery, development, and manufacture of polymeric nanoparticles.