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Chip Device Finds, Collects Circulating Tumor Cells

Labyrinth chip animation

(Joseph Xu, University of Michigan)

22 September 2017. A multi-disciplinary team designed a lab-on-a-chip device using hydrodynamic forces to find and help identify circulating tumor cells in blood samples. Researchers from the engineering and medical schools at University of Michigan in Ann Arbor, describe the device in the 20 September issue of the journal Cell Systems (paid subscription required).

The team from labs led by chemical engineering professor Sunitha Nagrath and cancer researcher Max Wicha who pioneered discovery of stem cells in cancer, are seeking more reliable techniques for capturing circulating tumor cells in blood. Circulating tumor cells are individual cells that break off from original tumors or those formed from where cancer spreads, and flow through the blood stream. These cells make up a minute proportion of blood volume, but are implicated in the spread of cancer to other parts of the body. Because of their tiny amounts, circulating tumor cells are difficult to find, but when detected can offer an early warning about the spread of cancer in a patient.

If reliable methods can be devised for capturing circulating tumor cells, they can offer immediate benefits to patients and clinicians, including the use of so-called liquid biopsies to detect and monitor the progress of cancer, instead of analyzing tissue samples requiring surgery from cancer patients. Nagrath, Wicha, and colleagues designed a lab-on-a-chip device using microfluidics, with tiny channels through which blood or other fluid specimens can flow, to capture these elusive cells.

The team call their device Labyrinth, since the channels in the clear plastic chip have a complex design almost resembling a maze. Doctoral candidate and first author Eric Lin who created the chip, fits 60 centimeters of channels into a 10-centimeter square design. But Labyrinth is designed to move blood samples through quickly, at 2.5 milliliters per minute, using hydrodynamics in the flow through the channels to separate and sort different types of cells.

The circular channels help separate the larger from smaller cells, with centrifugal force pushing the larger cells to the outside walls. Isolating smaller cells, however, are more of a challenge, which is the reason for sharp corners in the channel design. “Bigger cells, like most cancer cells, focus pretty fast due to the curvature, says Nagrath in a university statement. “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.”

In a proof-of-concept study, the team took blood samples already drawn from 76 breast and pancreatic cancer patients participating in a clinical trial. The samples were then sent through Labyrinth, with circulating tumor cells isolated from the rest of the blood. Results show the chip provides a high yield of circulating tumor cells, more than 90 percent, and with little contamination. Additional genetic profiling of the captured cells shows tumor cells representing a wide range of stem-cell qualities, which can help design more precise treatments for patients.

“We think that this may be a way to monitor patients in clinical trials,” notes Wicha. “Rather than just counting the cells, by capturing them, we can perform molecular analysis so [we] know what we can target with treatments.”

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