Stochastic Differential Scanning Calorimetry by Nonlinear Optical Microscopy

Stochastic phase transformations within individual crystalline particles were recorded by integration of second harmonic generation (SHG) imaging with differential scanning calorimetry (DSC). The SHG activity of a crystal is highly sensitive to the specific molecular packing arrangement within a noncentrosymmetric lattice, providing access to information otherwise unavailable by conventional imaging approaches. Consequently, lattice transformations associated with dehydration/desolvation events were readily observed by SHG imaging and directly correlated to the phase transformations detected by the DSC measurements. Following studies of a model system (urea), stochastic differential scanning calorimetry (SDSC) was performed on trehalose dihydrate, which has a more complex phase behavior. From these measurements, SDSC revealed a broad diversity of single-particle thermal trajectories and direct evidence of a “cold phase transformation” process not observable by the DSC measurements alone.