Separation of breast cancer cells from peripherally circulating blood using antibodies fixed in micro-channels
Bio-Micro Electro Mechanical System (Bio-MEMS) technology was applied to the problem of early breast cancer detection and diagnosis. A micro-device is being developed to identify and specifically collect tumor cells of low abundance (1 tumor cell among 107 normal blood cells) from circulating whole blood. By immobilizing anti-EpCAM (Epithelial Cell Adhesion Molecule) antibodies on polymer micro-channel walls by chemically modifying the surface of the PMMA, breast cancer cells from the MCF-7 cell line, which over-express EpCAM, were selected from a sample volume by the strong binding affinity between the antibody and antigen. To validate the capture of the breast cancer cells, three fluorochrome markers, each identified by a separate color, were used to reliably identify the cancer cells. The cancer cells were defined by DAPI + (blue), CD45 - and the FITC-cell membrane linker + (green). White blood cells, which may interfere in the detection of the cancer cells, were identified by DAPI + (blue), CD45 + (red), and the FITC-cell membrane linker + (green). EpCAM/anti-EpCAM binding models from the literature were used to estimate an optimal velocity, 2mm/sec, for maximizing the number of cells binding and the critical binding force. At higher velocities, shear forces (> 0.48 dyne) will break existing bonds and prevent the formation of new ones. This detection micro-device can be assembled with other lab-on-a-chip components for follow-up gene and protein analysis.
Publication Source (Journal or Book title)
Progress in Biomedical Optics and Imaging - Proceedings of SPIE
Feng, J., Soper, S., McCarley, R., & Murphy, M. (2004). Separation of breast cancer cells from peripherally circulating blood using antibodies fixed in micro-channels. Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 5 (1), 278-293. https://doi.org/10.1117/12.529748