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In pursuit of the deadly tumor cell

When a malignant tumor begins to grow somewhere in the body, it can take time—too much time—before it shows up on magnetic resonance imaging (MRI) or on released biochemical markers in the blood. The increased flow of blood around tumors, which are highly vascularized, makes it likely that some tumor cells will split off into the bloodstream and spread to other areas of the body before they are detected.

Metastatic cancer accounts for nine of every ten deaths from solid tumors, but the survival rate is high if the cancer is detected early. But what if a simple test could identify circulating tumor cells (CTCs) and alert physicians to the presence of the cancer before a mass shows up on a scan or before symptoms present?

A team led by Yaling Liu, associate professor of mechanical engineering and mechanics and also of bioengineering, has developed a promising technique for isolating the handful of CTCs that might be circulating among billions of normal blood cells in a single milliliter of blood. With a three-year grant from NSF, Liu and his collaborators are designing and testing a tiny “lab-on-a-chip” device that could make screening for CTCs part of a normal blood test.

“Early cancer detection has become a major focus of translational cancer research,” Liu says. And with good reason: The big C is the second-leading cause of death in the U.S., claiming more than 575,000 lives each year, almost as many as cardiovascular disease and four times more than lower respiratory disease, the third affliction on the list.

Many cancers are survivable if caught in time, but the Centers for Disease Control and Prevention says that nearly half of colorectal and cervical cancers and one in three cases of breast cancer go undetected until they are at an advanced stage.

CTCs could play a critical role in the quest by researchers to develop new techniques for early cancer detection. Many cancers express unique protein markers, such as CA 15-3, which indicates breast cancer, or prostate specific antigen (PSA), for which men are screened to detect prostate cancer. But blood contains millions of proteins, making it difficult to detect protein cancer markers. By contrast, blood contains only a few types of cells.

“It is relatively easier to detect a particular cell type,” says Liu, “and the results are more stable, too.”

A lab-on-a-chip performs tests on a microfluidic device smaller than a few square centimeters using as little as a few milliliters of fluid. Liu’s rectangular chip, made of the polymer PDMS, is about the length of two quarter coins. Its key feature is a tiny flow channel based on a hierarchically designed pad that is optimized to capture tumor cells from the blood flowing across it.

“Cells have protruding patterns,” says Liu. “We have tried to create patterns on the capture pad that are complementary with the patterns on CTCs.”

The low cost of Liu’s device—“You could build one for ten bucks,” he says—raises the potential that the device could be used for home tests or deployed in the developing world.

Read the story in the Vol. 1, 2015 issue of Resolve Magazine.

Yaling Liu
Yaling Liu
Yaling Liu
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