Life in slow motion: high-speed correlative fluorescence super-resolution and quantitative phase imaging

Many biological and soft-matter processes occur at high speeds in complex 3D environments, and developing imaging techniques capable of elucidating their dynamics is an outstanding challenge. Here, we introduce Fourier Synthesis Optical Diffraction Tomography (FS-ODT), a novel approach for quantitative phase imaging capable of recording the 3D refractive index at kilohertz rates. FS-ODT introduces pattern generation and inverse computational strategies that multiplex tens of illumination angles in a single tomogram, dramatically increasing the volumetric imaging rate. We demonstrate the capabilities of FS-ODT for probing complex systems by studying hindered diffusion of colloids and motility of bacterial swimmers. We further integrate FS-ODT into a multimodal microscope combining phase imaging with multicolor structured illumination microscopy. The resulting multimodal imaging platform unlocks challenging imaging regimes in biophysics and soft-matter that have been little explored, including the interactions of microswimmers with their viscous 3D environment and the interplay between these stimuli and the molecular response of biological systems.