Extracellular vesicles (EVs) from cancer cells remodel distant organs to promote metastasis in vivo. A biomimetic microsystem may compensate costly and time-consuming animal models to accelerate the study of EV organotropism. A tissue-based liver-kidney-on-a-chip is developed with precision-cut tissue slices (PTSs) cultured to represent individual organs. The organotropism of breast cancer EVs is modeled using the biomimetic microsystem. A traditional animal model of EV organotropism is used to investigate the physiological similarity of the microfluidic model to animal models. It is demonstrated that breast cancer EVs show strong liver tropism rather than kidney tropism on both the microfluidic and animal models. It isfound that the metastatic inhibitor AMD3100 inhibits liver tropism effectively in both the microfluidic and animal models. Overall, the tropism of EVs to different organs is reconstituted on the microfluidic model. The liver-kidney-on-a-chip may expand the capabilities of traditional cell culture models and provide a faster alternative to animal models for EV studies.

Intracellular calcium dynamics plays an important role in the regulation of vascular endothelial cellular functions. In order to probe the intracellular calcium dynamic response under synergistic effect of wall shear stress (WSS) and adenosine triphosphate (ATP) signals, a novel microfluidic device, which provides the adherent vascular endothelial cells (VECs) on the bottom of microchannel with WSS signal alone, ATP signal alone, and different combinations of WSS and ATP signals, is proposed based upon the principles of fluid mechanics and mass transfer. The spatiotemporal profiles of extracellular ATP signals from numerical simulation and experiment studies validate the implementation of our design. The intracellular calcium dynamics of VECs in response to either WSS signal or ATP signal alone, and different combinations of WSS and ATP signals have been investigated. It is found that the synergistic effect of the WSS and ATP signals plays a more significant role in the signal transduction of VECs rather than that from either WSS signal or ATP signal alone. In particular, under the combined stimuli of WSS and ATP signals with different amplitudes and frequencies, the amplitudes and frequencies of the intracellular Ca dynamic signals are observed to be closely related to the amplitudes and frequencies of WSS or ATP signals.

Cellular mechanical properties are promising biomarkers to indicate the disease states of patients. A quantitative method coupled with microfluidic chip was proposed to measure the apparent viscosities of single cells.