Non-invasive molecular detection using stimulated Raman spectroscopy and photo-acoustic detection

There is increasing interest in a (quasi-) continuous following up of body health parameters. Although several parameters can be addressed non-invasively, measuring the presence and/or concentration of specific biomolecules is still hard to accomplish. Nevertheless, optical spectroscopy does have the right capabilities. By scattering or direct absorption light can address molecular vibrations, that result in a unique fingerprint for (bio)molecules. Raman spectroscopy, for instance, exhibits molecular specificity and can be addressed using visible light sources and detectors. Broad deployment of this technique, however, is still hindered by both the dim Raman signals and the limited penetration depth of light in tissue,  mainly due to scattering. While a coherent, nonlinear Raman technique like stimulated Raman spectroscopy can strongly enhance the Raman signals, the detection problem can be tackled to switch to the so-called photo-acoustic detection, where light absorption is not measured through analysis of the reflected or scattered light, but by measurement of acoustic waves, generated in the tissue upon light absorption. Acoustic waves in the right frequency range can travel through tissue without notable scattering, allowing detection of light absorption of deep subsurface regions, which would be impossible using analysis the reflected light. This technique has been successfully demonstrated in a number of biomedical applications, for both imaging, spectroscopy and combinations of both. These demonstrations still typically require large instrumentation and/or suffer from low sensitivity of the used acoustic detectors.

Imec is working on different schemes for both light sources and highly sensitive acoustic transducers, not necessarily requiring direct contact with the skin/tissue, which would greatly increase the possible use cases of the technique. In this PhD project, you will focus on demonstrating this technology on relevant tissue phantoms and actual tissue by means of stimulated Raman scattering, which allows much deeper penetration than infrared spectroscopy, despite the weak signal.

Imec is soliciting enthusiastic PhD candidates to build and validate this technique using off-the-shelf and novel imec components. The goal of the PhD is to determine the ultimate limits of the technique, in terms of penetration depth and sensitivity.