Temperature-Modulated Micromechanical Thermal Analysis with Microstring Resonators Detects Multiple Coherent Features of Small Molecule Glass Transition.

Micromechanical Thermal Analysis utilizes microstring resonators to analyze a minimum amount of sample to obtain both the thermal and mechanical responses of the sample during a heating ramp. We introduce a modulated setup by superimposing a sinusoidal heating on the linear heating and implementing a post-measurement data deconvolution process. This setup is utilized to take a closer look at the glass transition as an important fundamental feature of amorphous matter with relations to the processing and physical stability of small molecule drugs. With an additionally developed image and qualitative mode shape analysis, we are able to separate distinct features of the glass transition process and explain a previously observed two-fold change in resonance frequency. The results from this setup indicate the detection of initial relaxation to viscous flow onset as well as differences in mode responsivity and possible changes in the primary resonance mode of the string resonators. The modulated setup is helpful to distinguish these processes during the glass transition with varying responses in the frequency and quality factor domain and offers a more robust way to detect the glass transition compared to previously developed methods. Furthermore, practical and theoretical considerations are discussed when performing measurements on string resonators (and comparable emerging analytical techniques) for physicochemical characterization.