Computational microscopy, i.e. the joint design of the imaging system and the reconstruction algorithms, has allowed us to circumvent trade-offs imposed by conventional microscopy methods. Computational microscopy methods (such as cryo-ET, super-resolution fluorescence, and quantitative label-free microscopy) enable new mechanistic studies or high-throughput screens. These methods build on a long history of qualitative imaging techniques that create contrast in largely transparent samples using known light-matter interactions. In this tutorial session, I will introduce label-free phase and polarization imaging through demonstrations and explanation of the underlying physical principles. I will discuss classical microscopy contrast methods and review how modern computational microscopy techniques build upon them. Lastly, I will demonstrate how our lab combines quantitative label-free phase and polarization imaging with fluorescence microscopy to study the dynamics of specific molecules of interest in the context of the overall architecture of live cells and organisms. Through large collaborative efforts at the Biohub, we aim to create an intracellular disease dashboard highlighting how cells respond to viral infection and to map the dynamic emergence of cell identity during development.
