The Birth of Crystals in Solution at Submillisecond Time Scales: Spinodal Decomposition into a Transient Viscoelastic Reactant-Rich Liquid

Abstract Understanding crystallization from solution is essential to natural and industrial processes. In contrast to the mechanism envisioned in classical nucleation theory, crystallization from solution frequently proceeds after liquid–liquid phase separation (LLPS) into transient reactant-rich liquid structures that subsequently convert into amorphous solids and crystals. Whether this initial LLPS occurs by nucleation or spinodal decomposition under given conditions is crucial since the two pathways set different physical environments for subsequent crystal nucleation. Existing data, from proteins and inorganic species, cannot discriminate between these mechanisms: submillisecond nanoscale characterization has remained beyond reach, so measurements could capture only late-stage coarsening, and mechanistic conclusions rest on thermodynamic inference from the phase diagram. Here, we capture reactant-rich liquid structures of cerium oxalate as they emerge, using small-angle X-ray scattering coupled to a microfluidic ultrafast mixer, achieving nanometer spatial resolution at reaction times as short as 200 μs. We show by direct structural characterization that under our conditions, these liquid structures form by spinodal decomposition: diffuse concentration fluctuations develop without induction time, precluding nucleation. Unexpectedly, coarsening dynamics reveals that the transient structures are viscoelastic, i.e., viscous at time scales of second, but elastic at the shorter time scales relevant to crystal nucleation. This viscoelasticity, contrary to nonclassical multistep crystallization theories where the transient matrix is described as a classical viscous liquid, governs coarsening dynamics and crystal nucleation within it. Viscoelastic spinodal decomposition requires a large viscosity contrast between coexisting phases, a condition met, or expected, in other systems, suggesting such effects may be widespread in crystallization.