FIP Seminar: Label-Free Chemical Imaging of Single-Cell Drug Response: From Subcellular Quantification to Super-Resolution

Drug discovery demands measurements that capture tumor heterogeneity, yet conventional assays report only ensemble averages. Stimulated Raman scattering (SRS) microscopy addresses this gap by directly probing drug distribution and phenotypic state in single cells, label-free and quantitatively. I will show how SRS enables longitudinal, subcellular measurement of drug uptake and efficacy in 2D cultures and 3D tumor spheroids, with machine learning applied to classify cell type and state from the resulting SRS images for content-rich screening.
To further elevate SRS capabilities for this application, I will present two orthogonal advances: a 4Pi-SRS interferometric scheme that improves axial resolution nearly sevenfold, and computational reconstruction methods that enhance spatial resolution and accelerate volumetric imaging. Together, these tools chart a route toward high-throughput, high-content, label-free drug screening in physiologically relevant models.