Thermomechanical characterization of single particles without the need for clean room fabricated devices

For the first time, a single particle of material can be used as a resonator!

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Thermal analysis is often used for characterization of materials. There exists a battery of thermoanalytical techniques that can be applied to ensure that an introduction of a new drug therapy will not be delayed due to unwanted or uncontrollable physical changes in drug compounds. The commonly used techniques, in early drug development, include; differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and dynamic mechanical analysis (DMA). These techniques provide valuable information about the physiochemical and mechanical stability of materials. However, these techniques have two main limitations (especially in cases where small amounts of pure material are available after synthesis); they require a minimum of several milligrams of material for analysis and give an averaged response of the measured material.

For a more fundamental understanding of materials, nano and micro-electromechanical systems (NEMS/MEMS) are being used by various research groups. The main benefits of using MEMS devices is that they require pico- to micro gram amounts of material for analysis and are very sensitive. However, up to now, scientists have had to rely on specialized cleanroom fabrication facilities to fabricate the devices that can be used for thermomechanical characterization. For scientists wishing to perform thermomechanical material characterization, it is challenging to get access to cleanroom facilities and there is a substantial cost associated with their use. This motivated the development of Particle Mechanical Thermal Analysis (PMTA), which overcomes this barrier and allows scientists to directly measure on a single drug particle (or any other material) of interest (Fig.1). For the experimental studies, theophylline monohydrate and collagen particles were first measured using standard techniques and then using PMTA. PMTA results were in agreement with standard techniques and detected additional thermal transitions.

The idea for this technique was inspired by drug needle particles that have a resemblance to micromachined structures such as microcantilevers. The example of the collagen particles was used to demonstrate the broad applicability of the technique and to provide new understanding of mass and mechanical changes at the particle level during heating.

There are challenges associated with PMTA. The main challenge, was ensuring that we were measuring the resonance frequency (fres) of the material (and not the substrate). In cases, where it was difficult to measure the fres, another particle had to be used. Moreover, it was sometimes challenging to track the fres of a material during its main phase transformation (i.e. dehydration of hydrates), due to the dampening that occurs in the material during such a process. The main benefits of PMTA are; simplicity, direct measurements on pure material, measurements in air (often NEMS/MEMS systems are operated in vacuum systems) and no need for cleanroom fabricated devices. Overall, we hope that scientists can use PMTA to investigate a variety of materials.


Fig. 1. Summary of this work. Single particles as resonators. Thermal analysis was performed on known samples using standard techniques and then compared to PMTA where the known samples (theophylline monohydrate & collagen particles) were treated as resonators during thermal cycling.

For more details, please refer to our recent publication in Nature Communications https://doi.org/10.1038/s41467...



Go to the profile of Peter Ouma Okeyo

Peter Ouma Okeyo

Post doc, Technical University of Denmark

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