Quantitative Phase Microscopy with Molecular Vibrational Sensitivity

Quantitative phase imaging (QPI) has become a valuable tool for studying optically transparent samples such as biological cells and tissues [1]. It yields the sample-specific optical path-length delay at each spatial point of the field of view with a nanometer resolution, enabling high-contrast and objective analysis. The major advantage of QPI is its wide-field, label-free measurement capability of the transparent morphology. This allows for high-speed imaging limited by the image sensor's frame rate while reducing optical and/or chemical damages to the sample which are troublesome in other imaging techniques such as fluorescence and Raman imaging. To date, QPI has been used for pathology diagnosis, phenotyping of live cancer cells, non-destructive measurement of cellular volume and dry-mass, study of cellular membrane dynamics, to just name a few. However, QPI lacks chemical sensitivity which limits its application to morphology-based diagnosis.