Chemical space for small molecule therapeutics discovery is greatly under-explored due to difficulties in animal testing, the first bottleneck compounds encounter in going from formula to human use. We developed and validated an assay that combines 3D tissue biofabrication with high-throughput imaging biomarkers. This may impact more diseases than just skin cancer, where we have recently shown promising preliminary findings. Our skin constructs have normal epidermis, with populations of human keratinocytes, dermis with human fibroblasts and tumor spheroids containing populations of human squamous cell carcinoma cells. We present imaging biomarkers that show the cellular chemotherapeutic treatment. This constitutes a novel chemotherapeutic assay that may enable a paradigm-shifting drug discovery pipeline. Such a pipeline could enable tissue-relevant assay on a high throughput scale and be both more robust than monolayer cell culture and easier than animal models.
The feasibility of using optical coherence tomography, a label-free, non-invasive technique, to monitor three-dimensional (3D) morphology and pathology of tumor spheroids has been previously demonstrated. Growth kinetics of each spheroid, with its size and volume measured, could be accurately characterized. However, the previous system was not fully optimized for the collection of spheroid data from the whole plate. Here, in a follow-up study, we demonstrated a high-throughput optical coherence tomography (HT-OCT) platform capable of performing automatic 3D imaging and analyses for all tumor spheroids in a multi-well plate. The total screening time for a 96-well plate was ~23 min, including the OCT acquisition time of ~3.2min. Employing HT-OCT system, we successfully characterized a plate of tumor spheroids modeling cell invasions, with 3 different drug treatments. The HT-OCT system can be a powerful tool for fast, robust 3D morphological characterization of simple and complex spheroids for different cancer models. Further, they can also be utilized to analyze other models like organoids and artificial skins.