Abstract
Coordination of cell populations through intercellular interactions is essential to the formation and function of living organisms. However, technologies enabling systematic dissection of cell-cell communications or manipulation of cell-cell interactions at the single-cell resolution remain largely out of reach. To solve this, a single-target pairing system, termed StarPair, is proposed, for the high-throughput and high-precision combination of desired single targets in droplets. How target buoyancy, target concentration, sorting parameters, droplet flow rates, and electric stimulation collectively determine the single-target pairing performance is comprehensively explored. Upon optimization of these parameters, pairing efficiencies over 95% can be achieved with an operation frequency reaching one million single-target pairs per 9.5 h for two-target assembly. Leveraging StarPair, the immune cell-cancer cell interactions are assessed between 4 × 10(5) cell pairs and the NK-92MI cells with high secretion capability are further enriched. It is envisioned that StarPair will open new perspectives for characterizing and manipulating cell-cell interactions at scale.