Microfluidic manipulation of the multicellular spheroids and organoids for modeling human diseases

Three-dimensional (3D) multicellular spheroids have emerged as powerful tools for modeling solid tissues and organs, offering superior recapitulation of human diseases compared to traditional 2D cultures. These self-assembled structures exhibit hierarchical organization that mirrors in vivo cellular behaviors, including metabolic activities, differentiation patterns, and complex intercellular interactions. The integration of microfluidic technologies has transformed spheroid research by enabling precise spatial-temporal control over the cellular microenvironment. This review examines how tailored microfluidic platforms facilitate the generation and manipulation of multicellular spheroids and organoids for disease modeling applications. We highlight recent advances in microfluidic devices that enable dynamic control, precise manipulation, and high-throughput analysis of 3D cellular constructs, with different modalities, such as microwell structure, micro droplets, micro traps, and external physical forces. Furthermore, we discuss the pivotal role of spheroids and organoids in developing microphysiological systems and organ on-chip platforms, which provide sophisticated in vitro models that better replicate the 3D tissue microenvironment and pathophysiology of human diseases. These technological developments represent a significant step toward more predictive preclinical models for drug screening and personalized medicine.