Sixian You

From photons to phenotypes: engineering label-free imaging for living systems

Live, label-free microscopy reveals cellular metabolism and dynamics in a way largely orthogonal to other biomedical imaging modalities. The ultimate dream is to directly phenotype cells in living patients for intraoperative imaging, ICU monitoring, and point-of-procedure screening. However, the gift of subcellular resolution and intrinsic contrast comes at the cost of depth, speed, and molecular specificity. This talk presents our recent efforts of pushing these limits by squeezing information from each pulse in the major sequences of imaging, i.e., illumination, detection, and computation. These include nonlinear fiber shaping and self-localized pencil beam for light delivery, single-pulse fluorescence lifetime microscopy for photon-efficient detection, and microenvironment-aware distillation \(MAD\) for phenotype decoding. I will show how these methods together enable studies of drug trafficking, nucleolar dynamics, and immune cell phenotyping, and discuss a path towards richer, faster measurements in living biological systems.