Using sound waves, an international team of researchers has developed a
gentle, contact-free method for separating circulating tumor cells from
blood samples that is fast and efficient enough for clinical use.
Circulating tumor cells (CTCs) are small pieces of a tumor that break
away and flow through the bloodstream. They contain a wealth of
information about the tumor, such as its type, physical characteristics
and genetic mutations.
The ability to quickly and efficiently harvest and grow these cells
from a blood sample would enable "liquid biopsies" capable of providing
robust diagnosis, prognosis and suggestions for treatment strategies
based on individual CTC profiling.
CTCs are, however, extremely rare and difficult to catch. There are
typically only a handful for every few billion blood cells running
through a patient's veins. And while there are many technologies
designed to separate tumor cells from normal blood cells, none of them
are perfect. They tend to damage or kill the cells in the process, lack
efficiency, only work on specific types of cancer, or take far too long
to be used in many situations.
In a new study, researchers from Duke University, MIT and Nanyang
Technological University (Singapore) demonstrate a platform based on
sound waves that is capable of separating CTCs from a 7.5-mL vial of
blood with at least 86 percent efficiency in less than an hour. With
additional improvements, the researchers hope the technology will form
the basis of a new test through an inexpensive, disposable chip.
Every year cancer claims the lives of millions of people around the
world and researchers are still searching for better tools for cancer
diagnosis, prognosis and treatment," said Tony Jun Huang, the William
Bevan Professor of Mechanical Engineering and Materials Science at Duke.
"Biopsy is the gold standard technique for cancer diagnosis," Huang
said. "But it is painful and invasive and is often not administered
until late in the cancer's development. With our circulating tumor cell
separation technology, we could potentially help find out, in a
non-invasive manner, whether the patient has cancer, where the cancer is
located, what stage it's in, and what drugs would work best. All from a
small sample of blood drawn from the patient."
The technology works by setting up a standing sound wave at an angle
to a fluid flowing through a tiny channel. Because sound is nothing more
than a pressure wave, this sets up pockets of pressure that push on
particles suspended in the liquid as they pass. This acoustic force acts
more strongly on the larger, more rigid cancer cells than on normal
blood cells, pushing the CTCs into a separate channel for collection.
The power intensity and frequency of the sound waves are similar to
those used in ultrasonic imaging, which is used safely in numerous
medical procedures. The risk of damage to the CTCs is reduced even
further because each cell experiences the acoustic wave for only a
fraction of a second and does not require labeling or surface
modification. These features give the technique the best possible chance
at maintaining the functions and native states of the CTCs.
The approach was first demonstrated three years ago in a
proof-of-concept study and has since been improved to the point where it
could be useful in a clinical setting. The result is a prototype device
that processes fluid at a rate of 7.5 mL/hour, seven times faster than
the original, without sacrificing any of its 86 percent efficiency or
numerous advantages over other methods.
"The biggest asset of this acoustic method of separation is that it's
very gentle on the circulating tumor cells," said Andrew Armstrong,
associate professor of medicine, surgery, and pharmacology and cancer
biology at the Duke University School of Medicine. "The cancer cells
remain viable after passing through the chip and can be characterized,
cultured or profiled, which allows us to do genotyping or phenotyping to
better understand how to kill them."
"The only FDA-approved technology for CTC detection
can only count and do basic characterizations of CTCs but cannot grow
CTCs outside of the body, because it basically kills the cells in the
process," Armstrong said. "Being able to get to these cells while
they're still alive gives us at least a chance at culturing them or
profiling them outside of the body to do the types of drug sensitivity
and genetic testing that may better inform therapy."
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