Single particles as resonators for thermomechanical analysis

Peter Ouma Okeyo,Peter Emil Larsen,Jukka Rantanen,Thomas Rades,Fatemeh Ajalloueian,Eric Ofosu Kissi,Anja Boisen

doi:10.1038/s41467-020-15028-y

Abstract

Thermal methods are indispensable for the characterization of most materials. However, the existing methods require bulk amounts for analysis and give an averaged response of a material. This can be especially challenging in a biomedical setting, where only very limited amounts of material are initially available. Nano- and microelectromechanical systems (NEMS/MEMS) offer the possibility of conducting thermal analysis on small amounts of materials in the nano-microgram range, but cleanroom fabricated resonators are required. Here, we report the use of single drug and collagen particles as micro mechanical resonators, thereby eliminating the need for cleanroom fabrication. Furthermore, the proposed method reveals additional thermal transitions that are undetected by standard thermal methods and provide the possibility of understanding fundamental changes in the mechanical properties of the materials during thermal cycling. This method is applicable to a variety of different materials and opens the door to fundamental mechanistic insights.

Highlights

Thermal methods are indispensable for the characterization of most materials
There are a number of analytical models that can be used to describe mechanical structures and the changes they undergo during thermomechanical analysis
dynamic mechanical analysis (DMA) shows a larger dehydration range of theophylline monohydrate (TP MH) compared to thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). These results show that the presented methods detect the main dehydration of TP MH, there are differences in the dehydration temperature ranges of DSC (ΔT = ~25 °C) and DMA (ΔT = ~30 °C) in comparison to Particle Mechanical Thermal Analysis’ (PMTA) (ΔT = ~11 °C)

Summary

Introduction

Thermal methods are indispensable for the characterization of most materials. the existing methods require bulk amounts for analysis and give an averaged response of a material. TGA is commonly used for water content determination[15] and can be useful for determining the dehydration pathway of hydrates, subtle thermal transitions, associated with metastable forms, are challenging to resolve/isolate All these noted techniques require a minimum of several milligrams of material for analysis and give averaged responses[16,17,18] that makes single particle analysis inaccessible. It is challenging to carry out a comprehensive evaluation if there is only a limited amount of material available, or when thermal transitions need to be resolved in heterogeneous samples during early preformulation[19] stage (drugs are often not pure[11,20,21,22] and contain the material of interest together with impurities or different solid-state forms)[22]. Various groups have demonstrated the benefits of small volume analysis versus bulk analysis in early drug development[24]

Methods

Results

Conclusion