Fast Brillouin microscopy for phase transition

Multiple human diseases ranging from neurodegenerative disorders (such as Alzheimer´s disease) to cancer have been found to be linked with biomolecular mechanical properties change (phase transitions PTs). While these diseases have impacted many human beings (50 million for only AD), the causes of most of these diseases are still mysterious, and there is yet no effective treatment. To understand the pathological role of PTs and their corresponding potential as a therapeutic target for these diseases, it is crucial to probe the mechanical properties of live cells. Current standard approaches to measuring the mechanical properties have important limitations: requirement of contact force (atomic force microscopy and optical coherence elastography) and lack of cellular resolution (ultrasound and magnetic resonance imaging). An emerging tool, Brillouin microscopy (BM), provides the capability of “imaging” the mechanical properties through probing the so-called Brillouin scattering spectrum in a non-invasive manner with 3D sub-cellular resolution. Its advent has led to a wide range of biological applications. However, the acquisition time for a standard confocal microscope size image is in the order of tens of minutes, owing to the trade-off between the measurement speed and the spectral resolution. Thus, it prevents the BMs from studying the kinetics of phase transitions in live cells. FaBriCATion is to substantially investigate in-vivo Brillouin microscopy, pushing the acquisition time to a sub-millisecond scale per spectrum while maintaining the high spectral resolution, therefore permitting the measurements of the dynamic changes in mechanical properties of the living cells and tissues in sub-cellular resolution. It will enable direct observations of biomolecular phase transitions and reveal their relationship with the pathological effects in cells. The project will advance the research in understanding biomolecular PTs, thus bringing economic and societal benefits.