In a new study published in Cell Systems, researchers said that a new chip etched with fluid channels sends blood samples through a hydrodynamic maze to separate out rare circulating cancer cells into a relatively clean stream for analysis.
Tumour cells isolated from blood samples have the potential to revolutionize cancer treatment by enabling doctors to plan customized treatments, monitor genetic changes, and flag the presence of aggressive cells that are likely to spread cancer. The trouble is that circulating cancer cells account for just one in a billion blood cells, and there weren't good options for accurately
Cancer stem cells are fluid in their gene expression, transitioning from stem-like cells that are good at surviving in the blood to more ordinary cell types that are better at growing and dividing. "The markers for them are so complex, there is no one marker we could target for all these stages," Sunitha Nagrath, who led the development of the chip.
The labyrinth technique was too imprecise to use on its own. Conventional chips, with spiral-shaped channels, left each cancer cell contaminated with thousands of other cells particularly white blood cells. The labyrinth riffs on the spiral, sorting the blood's contents according to the sizes of the cells, with smaller white and red blood cells accumulating in different parts of the fluid channel.
A number of forces are at play: on the inside of a curve, eddies push particles away from the wall. The larger cancer cells are pushed a bit harder than the smaller white blood cells. At the outside of the curve, smaller particles feel more drawn to the wall. Bigger cells, like most cancer cells, focus pretty fast due to the curvature. But the smaller the cell is, the longer it takes to get focused. The corners produce a mixing action that makes the smaller white blood cells come close to the equilibrium position much faster, Nagrath said.
The team could reduce the number of white blood cells contaminating the cancer cell sample by 10 times just by running the captured portion of the blood through a second labyrinth chip — a process that took only five extra minutes.
A thousand white blood cells mixed in with about 9 to 50 tumour cells might seem like a lot, but this level of contamination is manageable in the single cell analysis lab. The team analyzed individual cells to explore which genes were active — and which mutations were present — in the cancer cells.
Through genetic profiling, the team could pick out cells that were on their way to and from stem-like states, capturing the spectrum of cancer stem cells. They tested the chip with blood samples from pancreatic and late-stage breast cancer patients.
Monika Burness, a lecturer in haematology and oncology said the labyrinth chip is isolating cancer cells from the blood of patients with an aggressive form of breast cancer. The trial is investigating whether a treatment blocking an immune signalling molecule called interleukin-6 (helps heal wounds by temporarily activating adult stem cells) could make progress against cases of breast cancer that don't respond to standard treatments.