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Project

Overview

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).

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 phase transitions 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 by 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.

Phase transition of tau in neurons of Alzheimer´s disease brain.

    Impact

    FaBriCATion aims to tackle the intrinsic problem of the conventional SpBS-based Brillouin microscopy (BM): the trade-off between the acquisition time and the spectral resolution, to innovative and prominent lay the technological and methodological foundation for investigating phase transitions.

    The success of FaBriCATion will be a breakthrough for BM and a game-changer for research in phase transition pathological mechanics, which has been suffering from limited technological advancement for reliable measurements of mechanical properties in biological samples. This brings essential value to the study of neurodegenerative diseases, which has shown a close connection with biomolecular phase transitions.

    The successful implementation of FaBriCATion will lay the instrumental foundation for biologists and medical scientists to access the basics of phase transition with a radically new tool and offer the possibility of understanding the pathologies of numerous diseases relevant to a large population of human beings. Thus, it is expected to eventually contribute to the health of the people and the communities in the long term. On the other hand, considering the potential for scientific breakthroughs, the successful implementation of the project will certainly promote the competence and leadership of Europe in biophotonics and neuroscience research.