GHz acoustics for biosensing at single-cell level

GHz acoustics for biosensing at single-cell level

BACKGROUND

Mechanical and acoustic phenotyping has become an emerging field of research in biophysics and biomedical diagnostics, as cell stiffness and intracellular viscoelasticity are established biomarkers for cancer, immune activation, aging, and pathogen infection. There is rapidly growing interest in exploiting GHz acoustics for non-contact, non-invasive probing of single cells, detecting changes in biomolecular environments, and even accessing nanoscale properties of viruses.

Picosecond ultrasonics enables contactless, broad-bandwidth, sensing of elastic, mechanical, and acoustic properties of materials at the micro-nanoscale. The technology has been widely used for thin film characterization and now is being extensively explored for non-contact and non-invasive probing of single cells4 and even viruses. At KU Leuven and IMEC, expertise exists in picosecond ultrasonics, integrated photonics, micro- and nanofabrication, and lab-on-chip platforms. Combining these capabilities may open new pathways for detecting weak GHz acoustic signatures in fluidic media. This is an essential step toward characterizing soft biological matter and understanding biochemical pathways. However, the use of GHz ultrasonics in liquid environments remains technically challenging due to strong acoustic attenuation and complex wave interaction.

OBJECTIVES

The main objective of this thesis project is to investigate the feasibility of using optical interferometry to enhance the detection of GHz acoustic waves, exploring its applications towards sensing and identification of biological cells or small particles within a fluidic environment. Specific goals include:

• In‑depth review of the current understanding of how cellular mechanical properties arise from biophysical and biochemical pathways, e.g., cytoskeletal organization, membrane tension regulation, intracellular viscoelasticity, osmotic and ionic homeostasis, mechanotransduction pathways.
• Theoretical modeling acoustic nano-pulses’ propagation, reflection, scattering in layered systems.
• Experimental studying optical interferometric techniques (e.g., Michelson or Fabry–Pérot configurations) for detecting ultrafast acoustic waves.
• Assessing the potential of the technique for cell/particle detection and discrimination in microfluidic applications.

REFERENCES

1. Urbanska, M. & Guck, J. Single-Cell Mechanics: Structural Determinants and Functional Relevance. Annual Review of Biophysics 53, 367–395 (2024).

2. The force awakens in mechanomedicine. Nat Rev Bioeng 4, 205–205 (2026).

3. Matsuda, O., Larciprete, M. C., Li Voti, R. & Wright, O. B. Fundamentals of picosecond laser ultrasonics. Ultrasonics 56, 3–20 (2015).

4. Audoin, B. Principles and advances in ultrafast photoacoustics; applications to imaging cell mechanics and to probing cell nanostructure. Photoacoustics 31, 100496 (2023).

5. Zhang, Y. et al. Nanoscopic acoustic vibrational dynamics of a single virus captured by ultrafast spectroscopy. Proceedings of the National Academy of Sciences 122, e2420428122 (2025).