1. Labyrinth-like chip filters cancer cells from blood cells
Blood runs through the labyrinth chip, quickly separating cancer cells from white and red blood cells. [Image from Joseph Xu, Michigan Engineering]
The chip was designed with inspiration from the Labyrinth of Greek mythology and features fluid channels that send blood samples through a hydrodynamic maze. The labyrinth separates rare circulating cancer cells into a clean stream to be analyzed.
Separating tumor cells in blood samples helps doctors plan customized treatments, monitor genetic changes and identify aggressive cells that could potentially spread the cancer. However, circulating cancer cells are just one in a billion blood cells and aren’t good for capturing cancer stem cells accurately.
“You cannot put a box around these cells,” said Sunitha Nagrath, University of Michigan associate professor of chemical engineering and leader of the development of the chip, in a press release.
Cancer stem cells have a fluid gene expression. They can transition from stem-like cells that can survive in the blood to ordinary cells that are better at growing and dividing. Cell targeting doesn’t work well because it grabs the proteins that are known to be on the cell’s surface.
“The markers for them are so complex, there is no one marker we could target for all these stages,” Nagrath said.
The labyrinth chip uses a spiral to sort the blood’s contents by size of the cells. Smaller white and red blood cells gather in different parts of the fluid channels. Larger cells are pushed harder than smaller cells around the curves of the chip. On the outsides of the curves, smaller particles are 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.”
The research team was able to reduce the number of white blood cells by 10 times by running the blood through a second labyrinth chip in a process that only took an extra 5 minutes. The team could pick out cells that were in the process of transitioning from stem-like states and capture the spectrum of cancer stem cells.
The chip was tested with pancreatic and late-stage breast cancer blood samples.
“We think that this may be a way to monitor patients in clinical trials,” Max Wicha, one of the pioneers of the cancer stem cell hypothesis and one of the leaders of the development of the chip, said. “Rather than just counting the cells, by capturing them, we can perform molecular analysis so know what we can target with treatments.”
