Optimization of the high-throughput synthesis of multiblock copolymer nanoparticles in aqueous media: Via polymerization-induced self-assembly

Over the past fifteen years or so, polymerization-induced self-assembly (PISA) has become widely recognized as a powerful and versatile platform technology for the synthesis of a wide range of block copolymer nanoparticles of controlled size, shape and surface chemistry. In the present study, we report that PISA formulations are sufficiently robust to enable high-throughput experiments using a commercial synthesis robot (Chemspeed Autoplant A100). More specifically, we use reversible addition-fragmentation chain transfer (RAFT) aqueous emulsion polymerization of either n-butyl methacrylate and/or benzyl methacrylate to prepare various examples of methacrylic multiblock copolymer nanoparticles using a poly(methacrylic acid) stabilizer block. Adequate stirring is essential to generate sufficiently small monomer droplets for such heterogeneous polymerizations to proceed efficiently. Good reproducibility can be achieved under such conditions, with well-defined spherical morphologies being obtained at up to 45% w/w solids. GPC studies indicate high blocking efficiencies but relatively broad molecular weight distributions (Mw/Mn= 1.36-1.85), suggesting well-defined (albeit rather polydisperse) block copolymer chains. These preliminary studies provide a sound basis for high-throughput screening of RAFT-mediated PISA formulations, which is likely to be required for commercialization of this technology. Our results indicate that methacrylic PISA formulations enable the synthesis of diblock and triblock copolymer nanoparticles in high overall yield (94-99%) within 1-3 h at 70 °C. However, tetrablocks suffer from incomplete conversions (87-96% within 5 h) and hence most likely represent the upper limit for this approach.