3-D Nanostructures Capture Rare Tumor Cells in Blood
Perhaps the earliest sign that cancer is starting to spread is the appearance of so-called circulating tumor cells, or CTCs, in the blood stream. These are the forward army of a metastatic tumor, the cells that escape from the primary tumor and colonize other organs in the body. Having a fast, inexpensive method for capturing these rare cells from human blood could provide valuable information that would likely improve therapy, but current CTC assays are not quite up to this task.
That situation may soon change. In a report published in the journal Angewandte Chemie International Edition, a research team at the California Institute of Technology's NanoSystems Biology Cancer Center, led by Hsian-Rong Tseng, Ph.D., describes a device made of millions of nanoscale silicon pillars that gently captured over 40% of the CTCs added to samples of human blood. The capture process takes a mere 45 minutes and leaves up to 90% of the trapped cells alive for further analysis.
Tseng and his colleagues prepared their device using the standard lithographic tools developed for making computer chips. After creating a forest of nanopillars on a silicon wafer, the investigators then coat the surface of the pillars with an antibody that recognizes a molecule on the surface of CTCs known as EpCAM, or epithelial-cell adhesion molecule. EpCAM plays a role in helping CTCs stick to the lining of blood vessels, enabling these metastatic cells to escape the blood stream and eventually colonize organs such as the liver and bone. When CTCs are applied to the device, they respond to the presence of the EpCAM antibody by sending out hair-like projections that appear to interact strongly with the silicon nanopillars and enhance the CTC capture efficiency. In contrast, CTCs captured on a flat silicon structure do not produce these projections.
This work, which is detailed in a paper titled, "Three-Dimensional Nanostructured Substrates toward Efficient Capture of Circulating Tumor Cells," was supported by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. Investigators from MagArray Inc., also participated in this study. An abstract of this paper is available at the journal's Web site.