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.