Phase Imaging Across Length and Depth Scales for Biophysics and Medical Applications

Phase contrast optical imaging allows enhanced contrast with imaging geometries that utilize the wave nature of light. Optical instrumentation and computational imaging algorithms are

combined in quantitative phase imaging and achieve enhanced contrast. First demonstrated in 1930 by Fritz Zernike, phase contrast microscopy is now widely used in laboratories. These optical phase microscopes have diffraction-limited resolution imposed by optical wavelengths as well as limited penetration/imaging depth that constrains their applications.

Phase imaging with electrons and X-rays address some of these challenges at two extreme imaging depth scales. Accelerated electrons in electron microscopes can be used to probe much smaller length scales than in an optical microscope. Biological macromolecules otherwise invisible in transmission electron microscope becomes visible when a phase contrast imaging geometry is used. Likewise, soft and hard X-ray imaging systems are also explored for phase contrast imaging at much larger imaging depths compared to electron and optical microscopes. Some critical advantages of X-ray phase imaging are improved contrast in soft-tissue imaging for applications like early stage cancer detection or microcomputed tomography. In this talk, I will connect the principles, challenges and opportunities of phase imaging (optical, electron and X-ray) across length scales. In both electron phase microscopy and X-ray phase imaging, radiation sensitivity and imaging time becomes a major consideration. I will describe recent efforts to combine novel detectors, instrumentation and algorithms to overcome some of these limitations.