The main challenge in the isolation of circulating tumor cells (CTCs) resides in their extreme rarity in blood. Here we report on the design of efficient and disposable microfluidic CTC capture devices based on the plasma functionalization of PDMS and its subsequent conjugation with the anti-epithelial-cell adhesion-molecule (EpCAM) mAb. Model studies on planar surfaces demonstrated excellent immuno-specificity of cancer-cell capture using NCI H69 small-cell lung cancer cells and SK-Br-3 breast cancer cells. Taking advantage of the transparency of the PDMS device, direct observation of the capture events on the internal 3D microstructure of the device could be achieved. At a flow rate of 16 μL min−1, an overall capture efficiency of 80 to 90% is determined in cell-spiking experiments in PBS. In accordance with direct microscopic observations, an increased flow rate (48 μL min−1) only has a minor effect (30% reduction) on cell-capture efficiency. Capture efficiency of the device using cancer cells spiked in whole blood is above 70%. The combination of soft lithography and plasma-based functionalization described in this work enables the facile fabrication of efficient and disposable CTC capture devices based on PDMS, which could facilitate the transition of this new technology into the clinical environment. ; Mahaveer D. Kurkuri, Fares Al-Ejeh, Jun Yan Shi, Dennis Palms, Clive Prestidge, Hans J. Griesser, Michael P. Brown and Benjamin Thierry