A Microfluidic Droplet Array Promotes Trastuzumab Sensitivity Exploration of Single Breast Cancer Cells

Abstract Drug sensitivity is a major determinant influencing the efficiency of cancer treatment, and its evaluation faces critical challenges due to the cancer cell heterogeneity. Herein, a droplet‐driven compartmentalization array (SCell ^EV chip) is presented to uncover single‐cell trastuzumab sensitivity. Leveraging the differential flow resistance principle, the chip enables the flexible generation of single droplets orderly situated at designated spots. The single droplet includes parallel hydrodynamic microtraps empowers efficient compartments for single cell capture, and culture, and employs apt _CD63 ‐functionalized microbeads to immune‐affinity capture single cell extracellular vesicles (EVs). The pairing capture of single cells and their EVs using single beads allows simultaneous identification of EVs and their original cells. The protein profiles (HER2 and CD63) and anti‐cancer drug challenge revealed the cellular/EVs secretion heterogeneity at the single cell level and cell susceptibility to trastuzumab, further confirming that this chip achieves discriminating and predicting single breast cancer cells with different trastuzumab sensitivity using single cell/EVs profiling strategy. Furthermore, this analysis process retains the cell viability of measured cells to promote downstream detection integration. Overall, the SCell ^EV chip offers new avenues for single‐cell analysis and exhibits great potential for cancer diagnostic and targeted treatment.