Using bead injection to model dispensing of 3-D multicellular spheroids into microtiter plates

Biomedical translational research has relied on two dimensional (2D) cell cultures for drug discovery over the decades, requiring cells to grow on a flat surface which does not always accurately model in vivo biological states. Three dimensional (3D) cell cultures, also known as 3D spheroids or organoids, grow as cellular tissues that are more physiologically relevant especially with respect to emulating cancer tumor-like structures [1]. While attractive, current methods for generating 3D spheroids has yet to replace 2D culturing methods used for drug discovery efforts that employ high-throughput screening (HTS), having limitations with scalability, reproducibility, and compatibility predominantly associated with conventional microtiter plate usage. Presented is a novel use of bead injection for the reproducible placement of spheroids and beads into high density microtiter plates of a 384- and 1536- well format.