‘Nano-Velcro’ microfluidic chip. Credit: UCLA. |
Circulating tumor cells, which play a
crucial role in cancer metastasis, have been known to science for more than 100
years, and researchers have long endeavored to track and capture them. Now, a
UCLA research team has developed a device based on Velcro-like nanoscale
technology to identify and “grab” these circulating tumor cells, or
CTCs, in the blood.
Metastasis is the most common cause of
cancer-related death in patients with solid tumors and occurs when these
marauding tumor cells leave the primary tumor site and travel through the blood
stream to set up colonies in other parts of the body.
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 perform a
“liquid” biopsy, allowing for early detection and diagnosis, as well
as improved monitoring of cancer progression and treatment responses.
In a study published in Angewandte Chemie, the UCLA researchers announce the successful
demonstration of this “nano-Velcro” technology, which they engineered
into a 2.5-by-5–cm microfluidic chip. This second-generation CTC-capture
technology was shown to be capable of highly efficient enrichment of rare CTCs
captured in blood samples collected from prostate cancer patients.
The new approach could be even faster and
cheaper than existing methods, and it captures a greater number of CTCs, the
researchers said.
The prostate cancer patients were recruited
with the help of a clinical team led by physicians Dr. Matthew Rettig, of the
UCLA Department of Urology, and Dr. Jiaoti Huang, of the UCLA Department of
Pathology and Laboratory Medicine.
The new CTC enrichment technology is based
on the research team’s earlier development of ‘fly-paper’
technology, outlined in a 2009 paper 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 (lightning) speed,” said senior
study author Dr. Hsian-Rong Tseng, an associate professor of molecular and
medical pharmacology at the UCLA Crump Institute for Molecular Imaging and the
California NanoSystems Institute at UCLA.
“The cells bounce up and down inside
the channel and get slammed against the surface and get caught,” explained
Dr. Clifton Shen, another study author.
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 more user-friendly,
semi-automated interface that improves upon the earlier device’s purely manual
operation.
“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,” said Dr. Kumaran Duraiswamy, a
graduate of UCLA Anderson School of Management who became involved in the
project while in school. “When it reaches the clinic in the future, this
CTC-analysis technology could help bring truly personalized cancer treatment
and management.”
