Unveiling comprehensive cellular biophysical properties using quantitative phase digital holographic microscopy

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The human brain development displays species-specific features, in particular to generate the structures thought to be at the core of human-specific cognitive abilities, such as the cerebral cortex. However, the specific mechanisms underlying this neurodevelopment and leading to this complexity remain incompletely understood, primarily because of the poor experimental accessibility of the human embryonic brain. Nevertheless, recently, the development of technologies based on pluripotent stem cells (PSCs) have permitted to generate, from e.g. a simple skin biopsy of a healthy volunteer, all cell types that comprise his/her tissue including neuronal cells, which constitute the brain tissue. Considering that such generation process of human neuronal cells from PSCs in many ways recapitulates the development of embryonic neurons, its accurate study is providing unique new opportunities for the analysis of human brain development.******Obtaining a better understanding of this modeling human brain development in-vitro using PSCs technology represents the main objective of our research program achieved within the framework of the Canada Excellence Research Chair (CERC) in Neurophotonics. Toward this aim, we have been developing new multimodal optical microscopy techniques having the capacity to visualize accurately and non-invasively cells structure and dynamics during the generation process of human mature and functional neurons from PSCs.******Specifically, thanks to this research program, we plan to develop multimodal optical microscopy techniques, based on a holographic principle, having not only the capacity to visualize living cells in 3D but also to simultaneously provide information about cell biophysics and biochemistry. Indeed, recent work from a variety of fields has revealed that physical forces and biomechanical cell properties play as important a role in control of cell and tissue development as chemicals and genes. Practically, using such novel multimodal holographic microscopy techniques will make possible to address specifically questions concerning the measurement of cell biophysical properties in relation with the maturation of embryonic neurons into functional neurons. In addition, this multimodal capacity allowing grasping simultaneously several aspects of the multifaceted biological processes represents a promising approach to obtain a more comprehensive understanding of the basic mechanisms underlying the generation of functional neurons from PSCs.***Our research program, at the interface between optics, photonics and neurobiology mainly trains physicists, engineers, mathematicians and biologists, who combine their knowledge and skills to advance our understanding of the basic mechanisms of human brain development using PSCs and to improve our methods for advancing cell imaging.