New Device: Capture of Circulating Tumor Cells


Photo: Device

Antigen-independent cell sorting begins by tagging the white cells in a blood sample with magnetic beads;

A new system for isolating rare circulating tumor cells (CTCs) – living solid tumor cells found at low levels in the bloodstream – shows significant improvement over previously developed devices and does not require prior identification of tumor-specific target molecules.

Developed at the Massachusetts General Hospital (MGH) Center for Engineering in Medicine and the MGH Cancer Center, the device rapidly delivers a population of unlabeled tumor cells that can be analyzed with both standard clinical diagnostic cytopathology and advanced genetic and molecular technology.

"This new technology allows us to follow how cancer cells change through the process of metastasis," says Doctor Mehmet Toner. "Cancer loses many of its tissue characteristics during metastasis, a process we have not understood well. Now for the first time we have the ability to discover how cancer evolves through analysis of single metastatic cells, which is a big step in the war against cancer."

The new device – called the CTC-iChip – is the third microchip-based device for capturing CTCs developed at the MGH Center for Engineering in Medicine. The first two systems relied on prior knowledge of a tumor-specific surface marker in order to sort CTCs from whole blood and required significant adjustment for each different type of cancer. The systems also required four to five hours to process a single blood sample.

Combining elements of both approaches – magnetic labeling of target cells and microfluidic sorting – the CTC-iChip works by putting a blood sample through three stages. The first removes from the sample, on the basis of cell size, all blood components except for CTCs and white blood cells. The second step uses a microfluidic process developed at the MGH to align the cells in a single file, allowing for extremely precise and rapid sorting. In the third stage, magnetically labeled target cells – either CTCs tagged via the epithelial marker or white blood cells tagged on known blood-cell antigens – are sorted out. Tagging white blood cells instead of CTCs leaves behind a population of unlabeled and unaltered tumor cells and does not rely on the presence of the epithelial marker or other known tumor antigens on the cell surface.

The system was able to process blood samples at the extremely rapid rate of 10 million cells per second, handling a tube of blood in less than an hour. Both the mode of sorting out tagged CTCs, called tumor-antigen-dependent, and the technique that depletes white blood cells, called tumor-antigen-independent, recovered more than 80 percent of tumor cells from different types of cancer that had been added to blood samples. Comparison of the antigen-dependent-mode CTC-iChip with existing commercial technology for processing blood samples from patients with prostate, breast, pancreatic, colorectal and lung cancer showed the CTC-iChip to be more sensitive at detecting low levels of CTCs.; Source: Massachusetts General Hospital