"Ever since the invention of the microscope in the 17th century, it has been observed that live cells are transparent under visible illumination, i.e. they do not absorb (or scatter) light significantly. Thus, a magnified image of cells will generally exhibit low contrast. In order to overcome this difficulty, researchers have used exogenous (extrinsic) contrast agents that bind at various sites in the cell and render the structures visible. In the 1930s, Zernike realized that, although cells are not highly absorbing, they produce significant changes to the wavefront of the incident light due to refractive index variations across the cell, i.e. cells are phase objects. This simply means that light travels with different velocities in different regions of the cell, or, equivalently, that light experiences different time (phase) delays across the cell.
Quantifying the optical phase shifts associated with cells gives access to information about morphology and dynamics at the nanometer scale. Scanning electron microscopy can produce quantitative images of cellular components with nanometer scale accuracy. However, this method requires heavy preparation, which prevents its applicability to live cells.
In order to obtain nanometer scale information from unperturbed live cells, we employed the principle of optical interferometry, where a probe light beam is compared (interfered) with a reference beam. Quantifying the phase difference between the imaging and the reference beams, detailed knowledge about cell motions is obtained."

-Taken from the MIT Spectroscopy Lab website. Retrieved 12-30-12 at 8:00 AM.