Active neurons tends to have a different dynamical behavior compared to resting ones. Non-exhaustively, vesicular transport towards the synapses is increased, since axonal growth becomes slower. Previous studies also reported small phase variations occurring simultaneously with the action potential. Such changes exhibit times scales ranging from milliseconds to several seconds on spatial scales smaller than the optical diffraction limit.
Therefore, QPI systems are of particular interest to measure neuronal activity without labels. Here, we report the development of two new QPI systems that should enable the detection of such activity.
Both systems can acquire full field phase images with a sub nanometer sensitivity at a few hundreds of frames per second.
The first setup is a synchronous combination of Full Field Optical Coherence Tomography (FF-OCT) and Fluorescence wide field imaging. The latter modality enables the measurement of neurons electrical activity using calcium indicators. In cultures, FF-OCT exhibits similar features to Digital Holographic Microscopy (DHM), except from complex computational reconstruction. However, FF-OCT is of particular interest in order to measure phase variations in tissues.
The second setup is based on a Quantitative Differential Interference Contrast setup mounted in an epi-illumination configuration with a spectrally incoherent illumination. Such a common path interferometer exhibits a very good mechanical stability, and thus enables the measurement of phase images during hours. Additionally, such setup can not only measure a height change, but also an optical index change for both polarization. Hence, one can measure simultaneously a phase change and a birefringence change.