Mar 9, 2011

Tiny ‘Velcro’ Can Nab Cancer Cells in the Blood

Tiny ‘Velcro’ Can Nab Cancer Cells in the Blood

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An integrated chip for detecting circulating tumor cells in blood collected from prostate cancer patients. Credit: Dr. Libi Zhao and Xiaowen Xu

Researchers have developed a device inspired by Velcro that "grabs" tumor cells circulating in a cancer victim's blood stream.

The device works at the nanoscale level to efficiently identify free-floating cancer cells and could aid both cancer research and treatment, scientists say.

Circulating tumor cells, or CTCs, play a crucial role in cancer metastasis, which is the most common cause of cancer-related death in patients with solid tumors. Metastasis occurs when marauding CTCs leave the primary tumor site and travel through the blood stream to set up colonies in other parts of the body.

CTCs have been known to science for more than 100 years, and researchers have long endeavored to track and capture them.

The current gold standard for determining the disease status of tumors involves the invasive biopsy of tumor samples, but in the early stages of metastasis, it is often difficult to identify a biopsy site. By capturing CTCs in blood samples, doctors can essentially perform a "liquid" biopsy, allowing for early detection and diagnosis, as well as improved monitoring of cancer progression and treatment responses.

"This new CTC technology has the potential to be a powerful new tool for cancer researchers, allowing them to study cancer evolution by comparing CTCs with the primary tumor and the distant metastases that are most often lethal," Kumaran Duraiswamy of UCLA, who is a co-author of a study published this month in the journal Angewandte Chemie, said in a statement.

In the study, the UCLA researchers announced the successful demonstration of their "nano-Velcro" technology, which they engineered into a 2.5-by-five-centimeter microfluidic chip that lets blood flow through its interior. This second-generation CTC-capture technology could be even faster and cheaper than existing methods, and it captures a greater number of CTCs, the researchers said.

The new CTC enrichment technology is based on the research team's earlier development of "fly-paper" technology, outlined in a 2009 paper also in Angewandte Chemie. The technology involves a nanopillar-covered silicon chip whose "stickiness" resulted from the interaction between the nanopillars and nanostructures on CTCs known as microvilli, creating an effect much like the top and bottom of Velcro.

The new, second-generation device adds an overlaid microfluidic channel to create a fluid flow path that increases mixing. In addition to the Velcro-like effect from the nanopillars, the mixing produced by the microfluidic channel's architecture causes the CTCs to have greater contact with the nanopillar-covered floor, further enhancing the device's efficiency.

"The device features high flow of the blood samples, which travel at increased speed," said senior study author Hsian-Rong Tseng, an associate professor of molecular and medical pharmacology at UCLA.

"The cells bounce up and down inside the channel and get slammed against the surface and get caught," explained study co-author Clifton Shen, also of UCLA.

The advantages of the new device are significant. The CTC-capture rate is much higher, and the device is easier to handle than its first-generation counterpart. It also features a semi-automated interface that’s easier to use and improves upon the earlier device's purely manual operation.

"When it reaches the clinic in the future, this CTC-analysis technology could help bring truly personalized cancer treatment and management," Duraiswamy said.

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