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

• Published in: Analyst (London) Vol. 14; no. 1; pp. 3565 - 3572
• Main Authors: Diéguez, L, Winter, M. A, Pocock, K. J, Bremmell, K. E, Thierry, B
• Format: Journal Article
• Language: English
• Published: England 21.05.2015
• Subjects: Antibodies, Immobilized - chemistry; Antibodies, Immobilized - immunology; Blood; Cell Separation - instrumentation; Circulating; Dimethylpolysiloxanes - chemistry; Enrichment; Flow Cytometry; Humans; Lab-On-A-Chip Devices; Leukocyte Common Antigens - immunology; Leukocytes - pathology; MCF-7 Cells; Microfluidics; Nanostructure; Neoplastic Cells, Circulating - pathology; Silicone resins; Tumors
• ISSN: 0003-2654; 1364-5528
• DOI: 10.1039/c4an01768d

Efficient isolation strategies not based on epithelial biomarker expression are required to enable non-biased 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®. 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. Depletion of >99.7% WBCs enabling tumor cell recovery from blood with nano-rough PDMS microfluidic negative enrichment devices functionalised with anti-CD45.