Efficient microfluidic negative enrichment of circulating tumor cells in blood using roughened PDMS

Efficient isolation strategies not based on epithelial biomarker expression are required to enable nonbiased enrichment of circulating tumor cells (CTCs). CTCs undergoing epithelial-mesenchymal transition (EMT) may be prognostically relevant, and importantly are not detected with conventional epithelial based approaches such as CellSearch (R). A method for the non-biased isolation of cancer cells within a peripheral blood sample utilizing microfluidic mixing PDMS devices functionalized with anti-CD45 is reported. The introduction of micro and nanoscale roughness using a single step treatment with sulfuric acid significantly increases the binding yield of white blood cells (WBCs) to the anti-CD45 conjugated surfaces. Up to 99.99% WBC depletion is achieved with a tumor cell recovery yield of 50%. This high level of CTC enrichment is expected to facilitate the detailed characterization of CTCs using for instance, imaging flow cytometry as demonstrated here.