Acoustic characterization of microgels as a proof of concept for differentiating liquid biopsy samples by health status

Distinct mechanical and physical differences, such as in stiffness and morphology, exist among bloodborne cells, offering a unique opportunity for diagnostic applications. These properties vary across cell types and can shift significantly in response to disease, making them valuable indicators of pathological states. These distinctive properties are potentially identifiable through acoustic techniques, where variations in the speed of sound through the cells monitor alterations in their morphology and stiffness. To evaluate these distinctive properties, this study uses gelatin-based microgels, fabricated from two different gelatin types to ensure mechanical variation, as simplified models of cells to explore the use of acoustics for detecting mechanical differences in cell-like micron-sized particles. Swept-Frequency Acoustic Interferometry (SFAI) was used to assess the sound speed in microgel samples. The results showed discernible and consistent differences between both microgel types and highlight SFAI as a robust method for evaluating mechanical differences in soft, micron-sized materials. These findings support the potential of acoustics as a non-destructive strategy for distinguishing differences in soft biomaterials and may aid future efforts in applying similar methods to complex biological samples.