As one of the most advanced in vitro drug screening platforms, tumor organoids require accurate pharmacosensitivity assessments to ensure reliable results. However, achieving accurate volume assessment of these 3D organoid models remains a challenge in traditional drug screening processes. Here, a label-free organoids photoacoustic imaging (LFOPI) system is introduced for high-resolution 3D imaging of tumor organoids. The capabilities of the LFOPI system are evaluated by monitoring structural transformations in melanoma organoids. The LFOPI system is further employed for volumetric drug screening of melanoma tumor organoids. Drug screening with cisplatin and temozolomide reveal that LFOPI-based organoid volume data correlates more strongly with viability trends (0.8627 and 0.9069) than traditional diameter-based methods (0.8190 and 0.7849). Additionally, immunotherapy drug screening demonstrates the capability of the system to precisely assess the 3D volumes of irregularly shaped organoids. This LFOPI system provides a promising method for label-free drug screening and personalized treatment.
Keywords: label free; photoacoustic imaging; precision medicine; tumor organoids; volumetric drug screening.
© 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.