Enantiomer-Specific Nucleation Phase Selection under Nonequilibrium Optical Trapping

Precise control of nucleation pathways under nonequilibrium optical trapping conditions remains a fundamental challenge. Here, we report an enantiomer-specific reversal in phase selection during the optical trapping-induced crystallization of binary systems containing acetaminophen and either l- or d-phenylalanine. Switching the handedness of circularly polarized light reverses the dominant product between a thermodynamically stable cocrystal and a metastable phenylalanine phase. In situ Raman spectroscopy reveals constant local stoichiometry during irradiation, indicating the absence of a macroscopic polarization-induced concentration gradient. Instead, the results are consistent with a proposed mechanism where phase selection is driven by a polarization-dependent kinetic bias under strongly nonequilibrium conditions. We propose that this bias originates from subtle differences in the residence dynamics of transient nanoscale clusters within the optical trapping field, which are statistically amplified over time. These findings highlight a sophisticated kinetic route for controlling crystallization beyond conventional thermodynamic strategies.