Microfluidic Femtosecond Laser-induced Nucleation of Supersaturated Aqueous D-Serine Solutions

Abstract

Crystallization plays a pivotal role in pharmaceutical manufacturing, yet conventional techniques often lack spatial and temporal control over nucleation, particularly for challenging molecules like amino acids. In this study, we present a microfluidic crystallization platform integrated with femtosecond laser irradiation to induce and regulate nucleation in supersaturated aqueous D-serine solutions. Through systematic screening of supersaturation levels, laser pulse energy, repetition rate, and flow rate, we demonstrate that crystal formation requires the synergistic action of confined flow and localized photomechanical stimulation. Neither microfluidic flow nor femtosecond laser irradiation alone was sufficient to initiate nucleation, while their combination enabled reproducible crystal generation. Notably, moderate supersaturation (σ = 0.059) and lower energy or flow conditions yielded larger, well-defined crystals, whereas increased laser intensity, repetition rate, or flow rate enhanced nucleation but suppressed crystal growth. These findings offer new insight into crystallization dynamics under ultrafast excitation and establish a tunable strategy for amino acid crystallization, with potential applications in solid form screening and drug development.