Evaluation of Cell‐Extracellular Vesicle Interaction Using a Microfluidic Microsystem ( ^Cell ExoChip)

Abstract Metastasis remains a misunderstood concept that contributes to ≈90% of cancer‐related deaths. Despite theories regarding the “Seed‐and‐Soil” hypothesis, many mechanisms of metastasis remain unclear. Recent research highlights exosomes as potential factors for preparing the microenvironment (soil) for organotropic metastasis. Cell‐secreted exosomes play key roles in intercellular‐communication by exchanging information in the form of proteins and nucleic acids. Additionally, tumor‐derived exosomes (TDEs) demonstrate organotropic tendencies, facilitating metastasis through cellular transfer of cancerous materials. However, the cellular uptake of exosomes and cell response to exosome interactions has yet to be thoroughly studied in respect to organotropism. To address this gap, the ^Cell ExoChip is developed, a microfluidic device that studies the organ‐preferred exosome‐cell interactions using cancer‐derived cells and exosomes. Utilizing the ^Cell ExoChip, lung cancer cells tend are offered to have the highest exosome uptake compared to bladder and breast cell lines, enhancing their ability to transfer material and influence physiological conditions. Then, the impact of certain organ‐derived exosomes are analyzed on the cell exosome secretion rate from cells of different organ‐types, revealing lung exosomes having an increase in metastatic tendencies through enhancing exosome secretion post‐uptake of exosomes from various organs. These novel findings fill a critical gap in understanding the role of exosomes in metastasis and the potential of using the ^Cell ExoChip for studying and predicating metastasis.