Comprehensive Screening of Conditions for Block Copolymer Nanoaggregate Formation via Automated DLS

A fully automated robotic synthesizer for the screening of amphiphilic block copolymer nanoparticle synthesis is presented. To reach this aim, block copolymer solutions are mixed in continuous flow with water, allowing for the automated variation of overall polymer concentration, mixing ratio of the water and organic solvent phase and the overall flow rate of the system. Particle sizes are monitored online via a commercial DLS instrument, and the obtained data is automatically analyzed. While the machine generally allows to produce particles with a 10% standard deviation, the control software performs automatic outlier detection based on measurement of data in triplicates, and repeats experiments until a statistically robust result is obtained. The synthesis platform was tested on 5 individual block copolymers, namely poly(ethyl methacrylate)-block-poly(2-(dimethylamino)ethyl acrylate) (PEMA75-b-PDMAEA50), polystyrene-block-poly(2-(dimethylamino)ethyl acrylate) (PS50-b-PDMAEA25), polystyrene-block-poly(poly(ethylene glycol) methyl ether acrylate) (PS40-b-PPEGMEA35, PS90-b-PPEGMEA23) and polystyrene-block-poly(2-hydroxy ethyl acrylate) (PS90-b-PHEA14), which were obtained from RAFT polymerization.