Dynamic optical coherence microscope integrated with cell-cultivation chamber enabled longitudinal and early-stage assessment of tumor spheroid-drug interaction

Abstract

Abstract We present an integrated system that combines dynamic optical coherence tomography (DOCT) with a small cell-cultivation chamber to enable high-sensitivity and high-temporal-resolution imaging of tumor spheroid’s drug response. Unlike conventional OCT-based volume measurement, which only captures late-stage morphological changes, our system captures early-stage changes in spheroid’s intracellular activity. The compact chamber, positioned beneath the DOCT probe, maintains a cell-culture environment (37 $$^\circ$$ C, 5% CO $$_2$$ ) while allowing frequent system access without disturbing the cultivation environment. The proposed system was used to monitor human breast cancer (MCF-7) spheroids response to doxorubicin hydrochloride, tamoxifen citrate, and paclitaxel over 100 hours at 4-hour intervals. While standard OCT-based volume measurement failed to detect early-stage drug concentration impacts, DOCT signals revealed statistically significant differences among the drug concentrations as early as 12 hours. Additionally, high-temporal-resolution imaging at 30-minute intervals over 100 hours revealed rapid and subtle changes in the spheroid morphology and DOCT signals. The results demonstrate that the proposed integrated system of DOCT and cultivation chamber provides a superior, early-readout platform for label-free anti-cancer drug testing compared to traditional structural OCT imaging.