‘Labyrinth’ chip separates cancer cells for tailored patient treatments

Customised cancer treatments for individual patients could be made possible with the use of a new maze-like chip that is etched with fluid channels in order to separate out blood samples containing cancer cells.

The developers say the chip works like a “hydrodynamic maze” and is already in use in a breast cancer clinical trial.

By isolating the tumour cells, doctors can plan customised treatments, monitor genetic changes, and flag the presence of aggressive cells that are likely to spread the cancer.

Circulating cancer cells typically only account for one in a billion blood cells, and previously there weren’t good options for accurately capturing cancer stem cells, which are thought to be especially aggressive and drug resistant.

“You cannot put a box around these cells,” said Sunitha Nagrath, University of Michigan associate professor.

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,” Nagrath said.

Size-based sorting gets around this problem and has been tried before in spiral-shaped channels. However, these typically group cancer cells with thousands of other types – particularly white blood cells.

The labyrinth chip takes the same basic idea from 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,” Nagrath said. “The corners produce a mixing action that makes the smaller white blood cells come close to the equilibrium position much faster.”

The tortuous route laid out in the new labyrinth chips means over 60cm of channel can fit on a chip that would only contain 10cm in a spiral layout.

Moreover, without the need to wait for cancer cells to bind with traps or markers, the blood flow through the chip was very fast.

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 nine to 50 tumour cells might seem like a lot, but this level of contamination is manageable in the single cell analysis lab. The team analysed 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.

“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.”

Chip-based medical diagnosis tools are a fast-growing field. IBM developed ‘lab-on-a-chip’ technology last year that is designed to detect, rather than treat, diseases like cancer.

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