Tissue dynamics spectroscopy for three-dimensional tissue-based drug screening

Tissue dynamics spectroscopy combines dynamic light scattering with short-coherence digital holography to capture intracellular motion inside multicellular tumor spheroid tissue models. The cellular mechanical activity becomes an endogenous imaging contrast agent for motility contrast imaging. Fluctuation spectroscopy is performed on dynamic speckle from the proliferating shell and hypoxic core to generate drug-response spectrograms that are frequency versus time representations of the changes in spectral content induced by an applied compound or an environmental perturbation. A combination of 28 reference compounds and conditions applied to rat osteogenic UMR-106 spheroids generated spectrograms that were crosscorrelated in a similarity matrix used for unsupervised hierarchical clustering of similar compound responses. This work establishes the feasibility of tissue dynamics spectroscopy for three-dimensional tissue-based phenotypic profiling of drug response as a fully endogenous probe of the response of tissue to reference compounds.