Here we present a microfluidics-based affinity purification-mass spectrometry (AP-MS) pipeline to identify protein-protein interactions (PPI) using minute amounts of input material. The use of this automated platform allowed us to identify the human cohesin and CCC complex from only 4 micrograms of input lysate, representing a ~50-100 fold downscaling compared to regular microcentrifuge tubes-based workflows. As such, our method holds great promise for future AP-MS applications in which sample amounts are limited.