Process intensification for the synthesis of ultra-small organic nanoparticles with supercritical CO2 in a microfluidic system

Submicronization of organic compounds is a challenging requirement for applications in the imaging and pharmaceutical fields. A new Supercritical AntiSolvent process with microreactor (mu SAS) was developed for nanoparticle (NP) synthesis. Tetrahydrofuran (THF) was used to solubilize a model organic molecule, tetraphenylethylene, and supercritical carbon dioxide (sc-CO2) was used as antisolvent. The solubility of TPE in the THF/CO2 system was first measured by in situ experiments. Then, NPs of TPE were prepared in various experimental conditions and characterized by transmission electron microscopy (TEM). Chosen experimental conditions led to NPs with a mean size of 9 +/- 3 nm. Experimental mu SAS results were compared with size distributions obtained by simulation, to obtain surface tension values, which are difficult to access by experiment alone. Simulations coupling Computational Fluid Dynamics (CFD) and Population Balance Equation (PBE) were performed under turbulent conditions in the high pressure microreactors. This coupled experimental and theoretical approach allowed a deep understanding of the mu SAS process and underlined the superior value of this technique for the preparation of NPs.