Interferometric Imaging for Cell Biology

Overview

Over the past decade powerful optical methods for probing and imaging biological cells and tissues have been developed. Advances have been made from the microscopic scale to imaging of the whole brain, breast and other organs of the body. Most of this development has been intensity-based, in which the light-tissue interaction is viewed as a stream of bullets (photons) impinging on tissue scatterers. In this picture, elastic scattering, the origin of tissue turbidity, is considered to be a randomizing process. This picture is embodied in Monte-Carlo simulations.

Although this intensity-based picture can provide useful information, it is fundamentally incomplete, as the phase of the light wave is not considered. The light-tissue interaction is fundamentally a wave phenomenon, and the electric field picture, in which both phase and amplitude are included, is the correct one. From this perspective, elastic scattering is a deterministic process, and in principle reversible, not randomizing. This E-field picture will impact on microscopy, tissue imaging and, in the long run, human body imaging.

In 1999, the Spectroscopy Laboratory embarked on a new direction of research to develop E-field based techniques for probing and imaging biological cells and tissues. We have developed a new class of instruments based on quantitative phase measurements. Since Frits Zernike was awarded the Noble prize in physics for invention of the phase contrast microscope in 1953, this instrument and its related techniques have been a cornerstone of every cell biology laboratory. In spite of their enormous value, however, phase contrast methods are inherently qualitative and lack specificity. A central part of our microscopy work has been the development of a methodology to obtain and exploit quantitative phase information. This has led to new scientific opportunities as well as practical laboratory instruments that extend phase microscopy to the realms of quantitative and three dimensional microscopy. We believe that a family of quantitative and tomographic phase microscopes will soon replace conventional phase contrast methods in every cell biology laboratory and the use of intrinsic contrast (particularly based on refractive index) will open a new era in biomedical microscopy in which fixation and staining of cells and tissues are no longer required. Furthermore, these instruments will find wide commercial and scientific use in industry and university research laboratories worldwide.

Currently, the Spectroscopy Laboratory has the following ongoing core and collaborative interferometry-based projects.

Core Projects:

1. Quantitative Phase Microscopy
2. Field-based Tomographic Phase Microscopy
3. Optical Detection of sub-nanometer motions in Biological Cells

Collaborative Projects:

1. Refractive Index Maps and Membrane Dynamics of Human Red Blood Cells
2. Tomographic Phase Microscopy and Spring Constants of Cholesterol Helical Ribbons