Nanoprecipitation through solvent-shifting using rapid mixing: Dispelling the Ouzo boundary to reach large solute concentrations

Abstract

Hypothesis: The addition of a non-solvent to a solute in good solvent solution leads to nanoprecipitation, which is the spontaneous formation of nanodomains. Yet, increasing solute concentration usually leads to the formation of macrodomains that quickly separate into a bulk phase, which is a severe process limitation. The corresponding concentration threshold, often termed as the Ouzo boundary, remains a mystery that could find its origin in the complex interplay between nanoprecipitation and mixing.

Experiments: We performed a systematic investigation of nanoprecipitation thermodynamics and kinetics as well as its interplay with mixing hydrodynamics for the hexadecane-acetone-water system, in the presence of the non-ionic C₁₆EO₈ surfactant. The binodal curve and its underlying tie-lines were obtained using Raman spectroscopy, allowing the computation of the spinodal curve. Kinetics were probed using a continuous flow setup that combines two sequential rapid mixers. The impact of mixing efficiency was probed systematically by varying the oil concentration for respectively slow and rapid mixing, while the uncoupling from mixing and nanoprecipitation was quantified by modifying systematically the flow rate in a continuous flow approach.

Findings: We elucidate the nature of the Ouzo boundary that marks the maximal solute concentration leading to nanoobjects. Rather than a thermodynamic boundary, as evidenced by its uncorrelation to the spinodal curve, it results from the coupling of nanoprecipitation and mixing when both processes occur within the same time range, leading to heterogeneous conditions and the escape of some objects to the macroscale. Increasing the solute concentration speeds up nanoprecipitation and thus requires increasingly faster mixing times to uncouple both processes. Accordingly, if the mixing efficiency is large enough, it is possible to dispel the Ouzo boundary and reach very large solute concentrations. Implementing rapid mixing strategies in continuous flow approaches is thus the solution to overcome the most stringent condition of nanoprecipitation and open the way to scale-up, while also providing efficient means to probe its fast mechanism. Overall, the simultaneous control of hydrodynamics and physical chemistry is thus key to boost up the Ouzo effect.

Keywords: Boundary; Continuous flow; Kinetics; Mixing; Nanoprecipitation; Ouzo; Phase diagram; Solvent-shifting.