Ultrasensitive phase-resolved imaging of cellular morphology and dynamics

Microscopy is an important imaging tool in modern clinical medicine and basic biomedical research. The retrieval of phase information from microscopic samples has a long history initiated by the development of the phase contrast microscope. This technique exploits the fact that optically thin samples such as cells diffract light secondary to local variations in optical index. Phase contrast microscopy has had an immeasurable impact by allowing the user to qualitatively visualize small, subcellular variations in optical index. Quantitative phase microscopy seeks to build upon the principles of phase contrast microscopy to extract quantitative measures relating to optical index, birefringence, motion, and flow. In addition to highlighting subcellular detail in unstained cells, quantitative phase techniques can measure picometer–scale cell motions, small changes in cell index, and even cytoplasmic flow. Because of its sensitivity to phase and its ability to reliably quantify and track changes in coherent wavefronts, interferometry has recently gained momentum as a technique for the implementation of quantitative phase microscopy. This chapter reviews interferometric phase contrast microscopy techniques, with an emphasis on broadband interferometric techniques which exploit the principles of OCT. Both the underlying theory as well biological applications are discussed. Although this chapter gives particular focus to biologically relevant applications, the methods are readily extendable for other, nonbiological applications.