Table 1.

Comparison of different technologies for the formation of multicellular spheroids

	Throughput	Spheroid formation time	Spheroid size	Cell-compatibility	Accessibility to spheroids
Pellet culture150	Single spheroid in a centrifuge tube	2 h incubation on a shaker is needed	Only for large (millimeter scale) spheroids	Hypoxia causes necrosis in the spheroid core	Spheroids are harvested for further culture
Spinner flasks/rotating wall vessel151	Cells aggregate into spheres at 1 × 106 cells ml−1 in 12 h.	12 h	Cannot control spheroid size	Cells may be damaged by shear forces	Easy to harvest spheroids, exchange medium, or add drugs
Hanging drop152	384 spheroids per run	Cells accumulate after 1 day	Controllable by adjusting the cell density	Good	Nontrivial to exchange medium or add drugs
Microfluidics/microwell153	200 spheroids per minutes	Spheroids formed in 1 day	Size-controlled	Good	Can exchange medium or add drugs; nontrivial to retrieve spheroids
Acoustic technology29	∼100 spheroids per hour, or more than 6000 spheroids per operation	Spheroids formed in several minutes to ~30 min	Controllable by adjusting the cell density	Good	Spheroids are harvested for further culture