Continuous synthesis of block copolymer nanoparticles via telescoped RAFT solution and dispersion polymerisation in a miniature CSTR cascade

Miniaturised continuous-flow reactors offer a safe, economical, and scalable route to explore the synthesis of high-value chemical products. In the context of polymer synthesis, precisely defined and tuneable products can be prepared via reversible de-activation radical polymerisation (RDRP) techniques such as reversible addition-fragmentation chain-transfer (RAFT), for which tubular reactors are commonly reported. Herein, we present a miniature continuous stirred-tank reactor (CSTR) cascade for continuous-flow RAFT polymerisation with active mixing throughout, which is found to perform close to a theoretical CSTR cascade for the polymerisations considered in this study. The performance of the reactor is evaluated for both the aqueous solution RAFT polymerisation of N,N-dimethylacrylamide (DMAm) and the RAFT dispersion polymerisation of diacetone acrylamide using a poly(DMAm) macromolecular chain transfer agent (macro-CTA). It was determined that the residence time distribution (RTD) is important for informing the properties of the resulting polymers, with more CSTRs resulting in a narrower molar mass distribution. For particle synthesis by polymerisation-induced self-assembly (PISA), a series of block copolymers were prepared in separate batch and flow experiments for which the particles obtained were found to vary despite comparable molecular weights. Towards the development of a high throughput screening platform, a multi-stage, telescoped tubular-CSTR cascade reactor configuration was applied for inline macro-CTA synthesis and subsequent block extension. Differences in product properties between the processing methods used supports the idea that polymers are so-called ‘products-by-process’; indeed different polymer products can be accessed from the same chemistry through the application of alternative synthesis approaches.