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Microfluidic device extracts rare tumour cells using sound

07 April 2015

A simple blood test might one day replace invasive biopsies thanks to a new device that uses sound waves to separate blood-borne cancer cells from white blood cells.

A schematic showing the high-throughput device for separating cancer cells from white blood cells (image: Carnegie Mellon/MIT/Penn State)

Carnegie Mellon University President Subra Suresh and fellow researchers from the Massachusetts Institute of Technology and The Pennsylvania State University report the latest advancement that brings their device one step closer to clinical use, in a paper published this week in the online early edition of the Proceedings of the National Academy of Sciences (PNAS).

Earlier attempts to develop such a device, while promising, proved to be far too slow for clinical use. But in the new paper, the researchers report the development and validation of a microfluidic chip that uses sound waves to separate circulating  tumour cells (CTC) from white blood cells, to be up to 20 times faster than prior attempts. This enables the use of the device for basic research and makes the idea that clinicians could remove intact circulating  tumour cells (CTCs) from a standard blood draw closer to becoming a reality.

Additionally, the researchers tested their device using patient samples for the first time. These tests proved that their method for separating CTCs from cancer cells is as effective as the current FDA-approved technique.

"Using computer modelling, we were able to significantly improve the chip's throughput, and with further refinements, this device could enhance our ability to diagnose and treat cancer," says Suresh. "The current gold-standard for finding CTCs requires scientists to tag the cells using antibodies. Our technique has the added advantage of being label-free, without the need for any tagging that could chemically alter the cells. Our new approach would allow scientists and clinicians to gain more information on cell pathology and cancer metastasis than is currently possible."

In many cases, CTCs are too rare to be detectable because there might be only one CTC among hundreds of thousands of white blood cells. Currently, most researchers find and isolate the travelling  tumour cells either by using fluorescence and magnetic techniques or by mechanical means. Some of these methods require the cancer cells to be tagged using antibodies, which can alter the cell's genetic and physical make-up.

Other research groups have developed ways to remove CTCs using strong mechanical forces, which also can damage the cells. While all of these techniques allow researchers to count the number of CTCs in a blood sample for possible cancer diagnosis, researchers often can't use the altered cells to perform any additional functional tests reliably.

The new device could help to solve this problem. It doesn't require the use of any damaging tags. It uses only a gentle mechanical force created by sound waves, allowing scientists to recover whole, unaltered CTCs that are ready for further testing. The authors also have demonstrated that, at the cell level, the device preserves the integrity of the separated CTCs, somewhat similar to the gentle way in which ultrasound has long been used in medical imaging and diagnostics.

Using computer modelling and parametric numerical simulations the researchers were able to find ways to alter the device to make it more efficient - particularly the channel geometry and both the angle and width of the acoustic transducers. The most efficient prototype developed in this way processed a sample 20 times faster than the original, taking around five hours to process a 5ml sample.

The increased speed of the device makes it ready to use for laboratory research, but researchers warn that it's still too slow for broad clinical use. They plan to continue to refine the device to make it more suitable for separating CTCs from a vial of blood in less than 30 minutes, which will make it more amenable to commercialisation. They also hope to develop a version of the device that can be used with whole blood samples, eliminating the need to remove the red blood cells.

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