From single cell analysis to 3D micro physiological systems: microfluidic tools integrating cancer cell targets for...

Natural killer cell is a critical cell type in our immune system. Its therapeutic potential in the development of novel cancer immunotherapy has been emerging. Microfluidic technologies capable of manipulating small volumes of fluid through microchannels are emerging tools for advancing our knowledge of natural killer cell biology. However, the rationale behind microfluidic device design, material choice, and the precise engineering of in vitro microenvironments has yet to be systematically assessed through the lens of complex NK cell biology using cancer cells as targets for activation. This comprehensive review assesses microfluidic technologies designed for the study of NK cell phenotype/function at a single cell level, migration dynamics in the presence or absence of biochemical cues, natural killer-target cell interactions, and observation of sophisticated cellular behavior (infiltration/cytotoxicity) in multi-factorial complex microenvironments. Step by step advances in device complexity such as the integration of acellular hydrogels or multicellular co-culture systems highlight the emerging need for higher resolution analysis of natural killer cell properties at the single cell, tissue, and organ levels. The progression of microfluidic technologies for advancing knowledge of natural killer (NK) cell biological mechanisms within the last twenty years. Figure was generated using BioRender.