A new chip etched with fluid channels that sends blood samples through a hydrodynamic maze to separate out circulating tumor cells into a relatively clean stream for analysis has been developed and is currently in use in a breast cancer clinical trial, according to a recent Cell Systems paper.
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. Conventional cell targeting, by grabbing proteins known to be on the cell's surface, doesn't work well. "The markers for them are so complex, there is no one marker we could target for all these stages," explained Sunitha Nagrath, University of Michigan associate professor of chemical engineering, who led the development of the new chip along with Max Wicha, the Madeline and Sidney Forbes Professor of Oncology at Michigan Medicine.
The team's newly developed high-throughput microfluidic labyrinth sorts 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," Nagrath said. "The corners produce a mixing action that makes the smaller white blood cells come close to the equilibrium position much faster."
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.
"We think that this may be a way to monitor patients in clinical trials," Wicha said. "Rather than just counting the cells, by capturing them, we can perform molecular analysis so know what we can target with treatments."