Sound can separate cancer from blood cells

Researchers
have created a novel device that can rapidly isolate circulating tumor cells
from patient blood samples using sound. The breakthrough will decrease the time
and cost of detecting cancer. Separating circulating cancer cells from blood
cells for diagnostic, prognostic and treatment purposes may become much easier
using an acoustic separation method and an inexpensive, disposable chip, claim
a team of engineers. “Looking for circulating tumor cells (CTC) in a blood
sample is like looking for a needle in a haystack,” said Tony Jun Huang,
professor of engineering science and mechanics. “Typically, the CTCs are about
one in every one billion blood cells in the sample.”

This is a photograph of an acoustic tweezer device
about twice the size of a penny. Two sound transducers move the cells out of
the stream for separation.
(Credit: Tony Jun Huang, Penn State)
Existing
methods of separation use tumor-specific antibodies to bind with the cancer
cells and isolate them, but require that the appropriate antibodies be known in
advance. Other methods rely on size, deformability or electrical properties.
Unlike conventional separation methods that centrifuge for 10 minutes, surface
acoustic waves can separate cells in a much gentler way with a simple, low-cost
device. Acoustic-based separations are potentially important because they are
non-invasive and do not alter or damage cells.

“In
order to significantly increase the throughput for capturing those rare CTCs,
device design has to be optimized for much higher flow rates and longer
acoustic working length,” said Ming Dao, principal research scientist,
materials science and engineering, Massachusetts Institute of Technology. “With
an integrated modeling approach, the new generation of the device has improved
cell sorting throughput more than 20 times higher than previously achieved and
made it possible for us to work with patient samples.”

The
researchers worked both experimentally and with models to optimize the
separation of CTCs from blood. They used an acoustic-based microfluidic device
so that the stream of blood could continuously pass through the device for
separation. Using the differential size and weight of the different cells they
chose appropriate acoustic pressures that would push the CTCs out of the fluid
stream and into a separate channel for collection. The results appear in the
Proceedings of the National Academy of Sciences. Tilted-angle standing surface
acoustic waves can separate cells using very small amounts of energy. The power
intensity and frequency used in this study are similar to those used in
ultrasonic imaging, which has proven to be extremely safe, even for fetuses.
Also, each cell experiences the acoustic wave for only a fraction of a second.
In addition, cells do not require labeling or surface modification. All these
features make the acoustic separation method, termed acoustic tweezers,
extremely biocompatible and maximize the potential of CTCs to maintain their
functions and native states.

If
two sound sources are placed opposite each other and each emits the same
wavelength of sound, there will be a location where the opposing sounds cancel
each other. Because sound waves have pressure, they can push very small objects,
so a cell or nanoparticle will move with the sound wave until it reaches the
location where there is no longer lateral movement, in this case, into the
fluid stream that moves the separated cells along.
They
used two types of human cancer cells to optimise the acoustic separation ­ HELA
cells and MCF7 cells. These cells are similar in size. They then ran an
experiment separating these cells and had a separation rate of more than 83 per
cent from samples that had as few as one cancer cell per 1,00,000 white blood
cells. Physicians could use the devices to monitor how patients reacted to
chemotherapy, for initial diagnosis and for determining treatment. 
(Credit:Penn State)

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