Interaction between tumor-associated macrophages and tumor cells is crucial for tumor development, metastasis, and the related immune process. However, the macrophages are highly heterogeneous spanning from anti-tumorigenic to pro-tumorigenic, which needs to be understood at the single-cell level. Herein, a sessile microdroplet system designed for monitoring cellular behavior and analyzing intercellular interaction, demonstrated with macrophage-tumor cell pairs is presented. An automatic procedure based on the inkjet printing method is utilized for the precise pairing and co-encapsulation of heterotypic cells within picoliter droplets. The sessile nature of microdroplets ensures controlled fusion and provides stable environments conducive to adherent cell culture. The nitric oxide generation and morphological changes over incubation are explored to reveal the complicated interactions from a single-cell perspective. The immune response of macrophages under distinct cellular microenvironments is recorded. The results demonstrate that the tumor microenvironment displays a modulating role in polarizing macrophages from anti-tumorigenic into pro-tumorigenic phenotype. The approach provides a versatile and compatible platform to investigate intercellular interaction at the single-cell level, showing promising potential for advancing single-cell behavior studies.
In this work, a class of bubble-containing multicompartmental particles with self-orienting capability is developed, where a single bubble is enclosed at the top of the super-segmented architecture. Such bubbles, driven by potential energy minimization, cause the particles to have a bubble-upward preferred orientation in liquid, enabling efficient decoding of their high-density signals in an interference-resistant manner. The particle preparation involves bubble encapsulation via the impact of a multicompartmental droplet on the liquid surface and overall stabilization via rational crosslinking. The conditions for obtaining these particles are systematically investigated. Methodological compatibility with materials is demonstrated by different hydrogel particles. Finally, by encapsulating cargoes of interest, these particles have found broad applications in actuators, multiplexed detection, barcodes, and multicellular systems.
