Biophysics at the nanoscale using the intelligent multimodal optical microscope.

Advanced optical microscopes have been implemented in the last decades, shining a new light on the cellular and molecular biology questions. Multimodal optical microscopy is a growing attitude boosted by artificial intelligence that makes the microscope intelligent. In the era of super-resolved fluorescence microscopy, fluorescence plays a significant role, including its photochemical parameters, from brightness to lifetime, and non-linear approaches, like those associated with multi-photon excitation, also able to exploit intrinsic fluorescence and SHG/THG. In this framework, polarisation methods, like Mueller matrix microscopy, expand contrast mechanisms available for imaging toward label-free. The intelligent microscope is AI-guided through a computational core based on independent component analysis (ICA) un-supervised machine learning towards supervised deep learning. The ambitious target is to create a robust virtual environment "to see" what we could not perceive before. An interesting case study is related to understanding the role of chromatin remodelling in physiological/pathological processes.