Ultrasonic Endoscopes for DEEP Light Focusing

ongoing

Subcellular light focusing is the primary enabler of a number of characterization, diagnosis and treatment tools in biomedicine and life sciences, including microscopy and spectroscopy techniques or phototherapies. However, limited by the scattering of light, current approaches are only optimized to operate at depths below a fraction of a millimeter inside tissue. Deeper light focusing – which is fundamental for sound biological conclusions or accurate treatments –always comes at the expense of increased invasiveness, restricted sample availability, or loss of spatial or temporal precision. The overall objective of DEEP is to overcome the above limitations and develop an original non-invasive strategy to focus light inside tissue at a millimeter depth (or above) and in real-time while maintaining subcellular spatial confinement. Specifically, by exploiting the deep penetration of ultrasound and its ability to locally modify the optical properties of a sample, we will generate in-situ virtual endoscopes that will act as embedded optical lenses or waveguides inside living tissue, thus redirecting light toward a deeper focus. Throughout DEEP, we will implement a hybrid ultrasonic-optical system able to (i) generate ultrasonic endoscopes with particular shapes and propagation characteristics that maximize the coupling and guiding of light inside tissue; (ii) operate in synergy with cutting-edge imaging methods such as two-photon or optical-resolution photoacoustic microscopy to extend their imaging depth; (iii) analyze via fluorescence correlation spectroscopy the intracellular dynamics inside organoids at microsecond temporal resolution; (iv) combine laser-irradiation therapies with the real-time in-situ monitoring of the structural changes induced inside tissue. Ultrasonic-enabled virtual endoscopes will lead to an unprecedented control of light inside living systems, opening the door to transformative advances in personalized medicine and molecular biology.