There is an increasing interest in using three-dimensional (3D) cell structures for modeling tumors, organs, and tissue to accelerate translation research. Significant progress has been made in formation of such structures to recapitulate the in vivo environment but performing complex assays with them can be challenging. Organoids can be subject to loss or damage from pipettes during common steps such as media exchange, supernatant sampling, or immunofluorescence staining.  We present here a technical webinar to demonstrate the use of the Pu·MA System for automated assays with organoids or spheroids in Matrigel.