The use of optical phase in light microscopy has a rich and long history dating back to Zernike's invention of phase-contrast microscopy, for which he won the 1953 Nobel Prize. The Interferometric microscopy Lab at LBRC aims at developing field-based optical imaging modalities for biomedical applications. Of particular interest are studies related to cell growth and cell size regulation mechanisms; understanding the cellular basis of diseases such as malaria infection, sickle cell disease and cancer; and investigating the basic cell biology as in studying cell cycle dynamics and cellular biomechanics. Over the last two decades, the LBRC members have made several major technological advances in this area. These developments can be divided into three categorized as below:
The LBRC has developed several key wide-field interferometric microscopy systems for high-speed label study of biological cells. These include Hilbert phase microscopy, diffraction phase microscopy, speckle-field phase microscpy, dispersion phase microscopy, and polarization sensitive phase microscopy. The following highlights three sub-categories of wide-field transmission phase microscopy.
Optical diffraction tomography (ODT) provides volumetric structural and functional information of biological cells based on three-dimensional (3-D) refractive index distribution. The LBRC has developed ODT systems based on angle-scan, sample translation (synthetic aperture), and wavelength scanning. The following highlights technology developments in these three categories.
While transmission phase microscopy is a powerful tool for label-free imaging of cells and tissues, it requires the knowledge of refractive index (RI) of the sample to convert the measured quantitative phase maps into height maps. In addition, the measured phase shift is proportional to the refractive index difference, Δn, between the sample and the medium. In contrast, reflection mode interferometry yields phase measurements with measurement proportional to the index of refraction, n, leading to a sensitivity advantage of 2n/Δn. In the following, we highlight key technology developments in this category.