Studying Cell Dynamics using Quantitative Phase Imaging

Abstract

Most living cells do not absorb or scatter light significantly, i.e. they are essentially transparent, or phase objects. Phase contrast microscopy proposed by Zernike in the 1930's represents a major advance in intrinsic contrast imaging, as it reveals inner details of transparent structures without staining or tagging. While phase contrast is sensitive to minute optical path-length changes in the cell, down to the nanoscale, the information retrieved is only qualitative. Quantifying cell-induced shifts in the optical path-lengths permits nanometer scale measurements of structures and motions in a non-contact, non-invasive manner. Thus, quantitative phase imaging (QPI) has recently become an active field of study and various experimental approaches have been proposed.Recently, we have developed Spatial Light Interference microscopy (SLIM) as a highly sensitive QPI method. Due to its sub-nanometer pathlength sensitivity, SLIM enables interesting structure and dynamics studies over broad spatial (nanometers-centimeters) and temporal (milliseconds-weeks) scales. I will review our recent results on applying SLIM to basic cell studies, such as intracellular transport and cell growth. I will end with a discussion on new method, inspired from interferometry, for measuring cell-generated forces.